OBJECTIVE: To investigate the effect of tadalafil on the time to exercise-induced myocardial ischaemia in subjects with coronary artery disease (CAD). Background CAD and erectile dysfunction (ED) share similar risk factors. It is important to know the cardiovascular effects of tadalafil in patients with CAD during physical exertion that is comparable with sexual activity. METHODS: A randomized, placebo-controlled, double-blind, two-period, crossover study comparing the effects of tadalafil 10 mg and placebo on the time to exercise treadmill test (ETT)-induced myocardial ischaemia in subjects with stable CAD (n = 23; age range: 53-75 years, all exhibited ST-segment depression >1.5 mm at screening ETT at > 5METS). Haemodynamic responses to sublingual nitroglycerin (NTG) were assessed before and after ETT. RESULTS: Compared with placebo, tadalafil did not significantly affect the time to ETT-induced ischaemia (13 min/31 s vs. 13 min/36 s, respectively). Before exercise, NTG evoked decreases in sitting systolic blood pressure (SBP) that were significantly greater when subjects received tadalafil compared with placebo, and after exercise, more subjects experienced a decrease in SBP <85 mmHg in response to NTG after taking tadalafil vs. placebo. When subjects received tadalafil compared with placebo, SBP was lower at rest (-7 mmHg; -12,-2), during ETT (-10 mmHg; -16, -3), and after ETT (-13 mmHg; -19, -7). CONCLUSION: Tadalafil did not significantly alter the time to ETT-induced ischaemia compared with placebo in subjects with CAD. Tadalafil reduced resting and exercise SBP. Due to the potential for hypotension, the concomitant use of nitrates and tadalafil is contraindicated.