Dipyridamole increases adenosine levels and augments coronary collateralization in patients with coronary ischemia. This pilot study tested whether a 6-month course of sustained-release dipyridamole/aspirin improves coronary flow reserve and left ventricular systolic function in patients with ischemic cardiomyopathy. Six outpatients with coronary artery disease and left ventricular ejection fraction (LVEF) <40% were treated with sustained-release dipyridamole 200 mg/aspirin 25 mg twice daily for 6 months. Myocardial function and perfusion, including coronary sinus flow at rest and during intravenous dipyridamole-induced hyperemia, were measured using velocity-encoded cine magnetic resonance stress perfusion studies at baseline, 3 months, and 6 months. There was no change in heart failure or angina class at 6 months. LVEF increased by 39%+/-64% (31.0%+/-13.3% at baseline vs 38.3%+/-10.7% at 6 months; P=.01), hyperemic coronary sinus flow increased more than 2-fold (219.6+/-121.3 mL/min vs 509.4+/-349.3 mL/min; P=.01), and stress-induced relative myocardial perfusion increased by 35%+/-13% (9.4%+/-3.4% vs 13.9%+/-8.5%; P=.004). Sustained-release dipyridamole improved hyperemic myocardial blood flow and left ventricular systolic function in patients with ischemic cardiomyopathy.