The four ED pills compared: sildenafil, tadalafil, vardenafil and avanafil

Status: FDA-approved prescription medicine for ED (sildenafil, tadalafil, vardenafil and avanafil). Source: FDA-approved prescribing information on DailyMed, checked 2026-10-17.

In short: when men search for erectile dysfunction medication, they usually find four names, and plenty of products pretending to be a fifth. This page puts the four FDA-approved pills side by side using their own prescribing labels, then looks at what the American Urological Association (AUA) and a large pooled analysis say about whether one is better. Doses and timing are left out on purpose: those are set by the label and the prescriber for each man. Evidence level: approved drugs used for their labeled purpose, each backed by placebo-controlled trials; comparisons between them come mostly from pooled and indirect analyses, not head-to-head trials.

Figures come from the FDA prescribing information for Viagra, Cialis, vardenafil tablets and Stendra, and the Levitra entry in Drugs@FDA. Each label reports its own studies, so the rows sit side by side but are not a head-to-head test.

Which ED pills are FDA-approved?

Four pills are FDA-approved to treat erectile dysfunction, and all four belong to one drug class, the phosphodiesterase 5 (PDE5) inhibitors. They are sildenafil, first approved in 1998 as Viagra (Viagra label); tadalafil, approved in 2003 as Cialis (Cialis label); vardenafil, approved in 2003 as Levitra (Drugs@FDA, NDA 021400); and avanafil, approved in 2012 as Stendra (Stendra label). Each is a prescription medicine. Anything sold as an ED pill without a prescription, under another name, is not one of these four.

How do the four ED pills work?

All four work the same way: they block PDE5, the enzyme that breaks down cGMP, the chemical messenger that relaxes smooth muscle in the penis so blood can flow in during arousal. The Viagra label explains that arousal releases nitric oxide, which raises cGMP, and that sildenafil “has no direct relaxant effect” on the tissue; it only lets the natural signal last longer (Viagra label, section 12.1). The vardenafil and Stendra labels both state that “sexual stimulation is required for a response to treatment” (vardenafil label; Stendra label). Our explainer on how ED medications work walks through the chain step by step.

How do they differ?

The biggest practical difference is how long each one stays in the body. Sildenafil, vardenafil and avanafil are short-acting, with half-lives of about 4 to 5 hours, while tadalafil’s mean half-life is 17.5 hours (Cialis label, section 12.3). The Cialis label says tadalafil improved erectile function compared with placebo “up to 36 hours” after a dose, and it is the only one of the four also approved for the urinary symptoms of an enlarged prostate. The short-acting three differ in smaller ways: avanafil reaches peak blood levels fastest on its label, at a median of 30 to 45 minutes when fasted (Stendra label), against a median of 60 minutes for sildenafil and vardenafil. For the most common pairing in detail, see tadalafil vs sildenafil.

Does food change how they work?

A heavy, fatty meal slows three of the four, and tadalafil is the exception. The Cialis label says the rate and extent of tadalafil absorption “are not influenced by food” (Cialis label). With a high-fat meal, sildenafil’s peak arrived about 60 minutes later on average and was 29% lower (Viagra label), vardenafil’s peak level fell by 18% to 50% in two food studies (vardenafil label), and avanafil’s peak came about 1.1 to 1.25 hours later and 39% lower, with total exposure down only about 3.8% (Stendra label). The vardenafil and Stendra labels still say those pills may be taken with or without food.

How do the side effects compare?

The most common side effects overlap heavily. Headache, flushing, nasal congestion and back pain appear on all four labels’ lists of reactions reported in 2% or more of men, and indigestion appears on every list except avanafil’s (Viagra label, section 6.1; Cialis label, section 6.1; vardenafil label; Stendra label, section 6). A few entries stand out: abnormal vision, mostly a temporary color tinge, is on sildenafil’s list; muscle aches are on sildenafil’s and tadalafil’s; and sore throat or cold symptoms are on avanafil’s. Vardenafil’s label carries a distinct heart-rhythm caution: men with congenital QT prolongation, or who take class IA or class III antiarrhythmic medicines, “should avoid using” it (vardenafil label). Side-effect rates from different labels come from different trials, so they cannot be ranked against each other directly.

The labels also differ on emergency nitrates. If a doctor judges nitrates medically necessary in a life-threatening situation, the Cialis label says at least 48 hours should pass after the last tadalafil dose, the Stendra label says at least 12 hours after avanafil, and the Viagra label says “it is unknown when nitrates, if necessary, can be safely administered” after sildenafil (Cialis label; Stendra label; Viagra label). That is one reason a man with heart disease should tell any emergency team which ED pill he takes. Our page on the safest ED medication goes through what each label says for heart, kidney and liver conditions.

Is one ED pill the most effective?

No pill has been shown to be the most effective for every man, and the AUA says the three most-studied ones appear to work about equally well in the general ED population. In its discussion of Statement 8, the AUA says the PDE5 inhibitors, “particularly sildenafil, tadalafil, and vardenafil, appear to have similar efficacy in the general ED population,” and that relative efficacy is less clear for avanafil because the published literature is limited; its Appendix B1 plot shows active treatment groups clustering above placebo “without clear separation among medications” (AUA Erectile Dysfunction guideline). A 2015 network meta-analysis of 82 trials (47,626 men) did find a trade-off at starting doses: sildenafil had the greatest efficacy but the highest overall rate of side effects, tadalafil had intermediate efficacy and the lowest rate of side effects, and vardenafil and avanafil had side-effect rates similar to sildenafil with “markedly lower global efficacy” (Chen et al., European Urology, 2015). The AUA notes that the literature lacks trials comparing these medicines directly, so rankings like these describe groups, not what one man will experience.

So what is the best ED medication?

The best ED medication is the one that suits a particular man’s health, other medicines and preferences, and that is a decision made with a prescriber rather than from a ranking. The AUA’s guideline statements say men with ED “should be informed regarding the treatment option of an FDA-approved oral” PDE5 inhibitor, “including discussion of benefits and risks/burdens, unless contraindicated” (Statement 8), that instructions “should be provided to maximize benefit/efficacy” (Statement 9), and that “the dose should be titrated to provide optimal efficacy” (Statement 10) (AUA guideline). In practice that means a first pill that falls short is not the end of the road; how it was taken and the dose the prescriber set both matter. The label differences above, such as how long each lasts, how food affects it and which other medicines it interacts with, are the kind of detail that discussion can cover, along with how a man tolerated an earlier pill.

Are there generic versions of all four?

Yes. FDA-approved generic tablets for each of the four ingredients have labels on DailyMed: generic sildenafil, generic tadalafil, generic vardenafil and generic avanafil. Brand-name Levitra tablets are listed as discontinued in FDA records, with a Federal Register determination that they were not withdrawn for safety or effectiveness reasons (Drugs@FDA, NDA 021400). An approved generic carries the same active ingredient as the brand; our explainer on generic Viagra (sildenafil) shows what that means in practice. For the sildenafil side of that question, see what sildenafil is, and for avanafil’s own label and generic, see avanafil (Stendra).

What else is sold that is not approved?

Plenty, and none of it is one of the four approved pills. Compounded versions made by pharmacies are, in FDA’s words, “not FDA-approved,” which means FDA “does not verify the safety, effectiveness or quality of compounded drugs before they are marketed” (FDA, Compounding and the FDA: Questions and Answers). Products sold as supplements raise a different problem. FDA warns that many products claiming to treat sexual dysfunction, including “male enhancement supplements” and “erectile dysfunction treatments,” are “likely to be contaminated with dangerous hidden ingredients,” that they are sold online and in stores, and that they “can lead to severe health issues and hospitalization” (FDA, Sexual Enhancement and Energy Product Notifications). In one September 2026 notice, FDA lab testing found tadalafil not listed on a product’s label, and FDA warned the hidden drug “may interact with nitrates found in some prescription drugs such as nitroglycerin and may lower blood pressure to dangerous levels” (FDA, Candy Power For Man notice). Our page on FDA warnings about tainted supplements covers what the agency has found, and our guide to how to tell a real generic from a fake covers the checks that work.

Status: Dietary supplement: not FDA-approved to treat any disease. Compounded: not FDA-approved. Source: FDA, checked 2026-10-17.

When should you talk to a clinician?

Before starting any of the four, because each is a prescription medicine and ED itself can be a sign of other health problems. The AUA says men “should be counseled that ED is a risk marker for underlying cardiovascular disease (CVD) and other health conditions that may warrant evaluation and treatment” (AUA guideline, Statement 3). Bring a full list of medicines, including any nitrates, blood pressure or prostate medicines, heart-rhythm drugs, antifungals, antibiotics and HIV medicines, and mention any heart, eye, kidney or liver history. Get emergency care for chest pain after taking an ED pill, an erection lasting more than 4 hours, or sudden loss of vision or hearing. Which pill fits, and how to take it, is a decision for you and the prescriber.

Sources

1. Viagra (sildenafil citrate) tablets, prescribing information, Pfizer, DailyMed
2. Cialis (tadalafil) tablets, prescribing information, Eli Lilly, DailyMed
3. Vardenafil hydrochloride tablets, prescribing information, Lannett, DailyMed
4. Stendra (avanafil) tablets, prescribing information, Metuchen Pharmaceuticals, DailyMed
5. Drugs@FDA: NDA 021400, Levitra, US Food and Drug Administration
6. Sildenafil tablets (manufactured for Macleods Pharma USA, NuCare Pharmaceuticals listing), DailyMed
7. Tadalafil tablets, Teva Pharmaceuticals, DailyMed
8. Avanafil tablets, Camber Pharmaceuticals, DailyMed
9. Erectile Dysfunction: AUA Guideline, American Urological Association
10. Chen L et al. Phosphodiesterase 5 inhibitors for the treatment of erectile dysfunction: a trade-off network meta-analysis. European Urology, 2015
11. Sexual Enhancement and Energy Product Notifications, US Food and Drug Administration
12. Compounding and the FDA: Questions and Answers, US Food and Drug Administration
13. Candy Power For Man may be harmful due to hidden ingredient, US Food and Drug Administration