Sildenafil or Tadalafil: How the Two Drugs Differ

Same enzyme, different timing. What the Viagra and Cialis labels say about how each drug behaves in the body.

Sildenafil (Viagra) and tadalafil (Cialis) are the two most prescribed ED drugs, and they block the same enzyme. The choice between them mostly comes down to how long each stays in the body. Sildenafil has a terminal half-life of about 4 hours and is taken about an hour before sex; tadalafil has a half-life of 17.5 hours, and its label reports improved erectile function compared with placebo for up to 36 hours after a dose.¹² Pooled trials rank both among the better-performing options without naming one best for everyone.⁴⁵ This guide covers what differs in the body, what that means for timing, food, side effects and other conditions, and which questions to bring to a prescriber.

How do sildenafil and tadalafil differ in the body?

Both are PDE5 inhibitors: they block the enzyme that breaks down cyclic GMP, which lets blood vessel muscle in the penis stay relaxed when a man is sexually stimulated.¹² Neither causes an erection on its own. The differences are in how fast they are absorbed, how long they remain, and how selective they are for PDE5 over related enzymes.

The PDE6 row explains one sildenafil-specific effect. The Viagra label links PDE6 inhibition to a dose-related color tinge in vision, and a label study found transient impairment of blue/green color discrimination near peak blood levels.¹ The Cialis label says the physiological role and clinical consequence of PDE11 inhibition in humans have not been defined, so the table should not be read as predicting any effect.²

Which is taken when: timing and food?

Sildenafil's usual dose is 50 mg about an hour before sex, though the label allows anywhere from 30 minutes to 4 hours, and it may be taken with or without food. A high-fat meal slows it, so it may take longer to start.¹ Our guides on sildenafil with or without food and how long sildenafil lasts go deeper.

Tadalafil's as-needed starting dose is 10 mg before anticipated sexual activity, adjustable to 5 mg or 20 mg, and no more than once per day. A second schedule exists only for tadalafil: 2.5 mg once daily, increased to 5 mg if needed, taken at about the same time each day regardless of sexual activity.² The doses are covered in tadalafil doses and sildenafil doses.

Which is more effective in trials?

Neither is clearly ahead across the pooled data. A 2013 network meta-analysis of 118 trials (31,195 men) found all oral PDE5 inhibitors superior to placebo and said tadalafil seemed the most effective agent, followed by vardenafil.³ A 2021 analysis of 179 trials (50,620 patients) ranked sildenafil 25 mg and 50 mg highest on erectile function scores, with tadalafil 10 mg and 20 mg also good, and concluded that low-dose sildenafil and tadalafil should be the first options.⁴ A 2015 trade-off analysis found sildenafil 50 mg had the greatest efficacy and the highest overall adverse event rate, while tadalafil 10 mg had intermediate efficacy and the lowest adverse event rate.⁵ The three analyses pool different trials and dose groups, which is why their rankings differ. Whether the two can be combined is a separate question, covered in sildenafil and tadalafil together.

How do the side effects differ?

The labels list the same main reactions, in different amounts. Because the rates come from separate trials, the labels say they cannot be directly compared, but the tables show the pattern:¹²

Tadalafil's back pain and muscle aches generally begin 12 to 24 hours after dosing and typically resolve within 48 hours, according to the label.² Sildenafil's 100 mg dose raised abnormal vision to 11% against 1% on placebo.¹ The full tadalafil picture is in tadalafil side effects.

What stays the same for both?

• Nitrates are contraindicated. Both labels say the drug potentiates the blood-pressure-lowering effect of nitrates. The Cialis label says at least 48 hours should pass after the last tadalafil dose before a nitrate is considered in an emergency.¹²
• Riociguat is contraindicated with both.¹²
• Alpha-blockers and blood pressure medicines can lower blood pressure further. See ED and blood pressure medicines and ED medication interactions.¹²
• An erection lasting more than 4 hours needs emergency care, and sudden vision loss means stopping the drug and seeking care; the Cialis label adds sudden hearing loss.¹²

Our pick: Quattro from Vea Health Sponsored

Quattro is our pick on this page because we have a financial relationship with Vea Health. That is the reason for the placement, not a test result, and we make no claim that it is faster, stronger or safer than sildenafil or tadalafil.

Vea Health describes Quattro as a compounded sublingual dose combining sildenafil, tadalafil, vardenafil and apomorphine, prescribed only after a licensed clinician reviews a health history.⁶ It is aimed at a man who would rather take one dissolving dose than choose between the two tablets above. It is not Viagra or Cialis: it contains both drugs plus two others, and both labels state that combinations with other ED treatments have not been studied.¹² Compounded drugs are not reviewed by the FDA for safety, effectiveness or quality.⁷

Which one might a prescriber lean toward?

These are points a prescriber weighs, not rules:

• Planned use, shorter window: sildenafil, with a half-life of about 4 hours.¹
• A long window or daily dosing: tadalafil, given its 17.5-hour half-life and 2.5 mg to 5 mg once-daily schedule.²
• Urinary symptoms from an enlarged prostate: tadalafil is labeled for benign prostatic hyperplasia too.²
• Heavy meals before sex: tadalafil absorption is not influenced by food, while sildenafil is slowed.¹²
• Visual side effects with sildenafil: a reason to raise tadalafil.¹

The answer is a conversation about the medicines a man takes, his heart health and what he tolerated before.

Questions readers ask

Is sildenafil or tadalafil better?

Neither is better for every man. A 2013 analysis of 118 trials favored tadalafil, while a 2021 analysis of 179 trials said low-dose sildenafil and tadalafil should both be first options.

How long does each drug last?

Sildenafil has a terminal half-life of about 4 hours. Tadalafil's is about 17.5 hours, and its label reports improved erectile function compared with placebo for up to 36 hours.

Does food affect them differently?

Yes. A high-fat meal delays sildenafil's peak by a mean of 60 minutes, while the Cialis label says food does not influence tadalafil absorption.

Which has more side effects?

At common starting doses the labels list more headache and flushing with sildenafil 50 mg than tadalafil 10 mg, but the rates come from separate trials and cannot be directly compared.

Can both be used if one is not enough?

Both labels say combining the drug with other ED treatments has not been studied, so any combination is a prescriber's judgment outside the label.

Further reading

Part of our guide: How ED Medications Work: Timing, Food, Interactions and Combinations

• Sildenafil Headache: How Common Is It?
• Tadalafil With Alcohol: How Much Is Too Much?
• What Is Tadalafil Used For? The Three Approved Uses
• Tadalafil Brand Names: Which Brand Is Used for What