Abstract Objectives: To test the safety of sildenafil in patients with stable coronary artery disease (CAD). Methods: Sixty-one patients with stable CAD, documented by coronary angiography were included in this phase I study. Patients were randomized to either single dose sildenafil or matched placebo. Speckle tracking echocardiography was done at baseline and 60 min after sildenafil/pla-cebo intake to calculate peak systolic strain (PSS) of the most severely affected myocardial segments and the global longitudinal PSS. Results: The baseline mean segmental PSS in the sildenafil group changed by 52%, 3 ± 1% at baseline versus 7 ± 2% after sildenafil intake, P = 0.01. However, no significant changes were reported in the placebo group, 7 ± 3% at baseline versus 7.25 ± 3%, P = 0.1. The baseline mean global longitudinal PSS in the sildenafil group changed by 9% (15 ± 4% at baseline versus 18 ± 3% after sildenafil, P = 0.03). In placebo patients, the change was only 3% from baseline (14.8 ± 2% at baseline compared to 15 ± 2% after placebo intake, P = 0.1). Sildenafil was well tolerated without clinical or hemodynamic deterioration after its intake. Conclusion: Sildenafil intake is safe in patients with stable CAD, it induced marginal improvements in the peak systolic strain of different myocardial ischemic territories.