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/placebo 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.