Human endothelial progenitor cells (EPCs) can differentiate into cardiomyogenic cells in vitro. We tested the effects of statin therapy on the differentiation rate of EPCs from patients with coronary artery disease (CAD), who may benefit from autologous cell therapy.EPCs from 3 age-matched groups were tested: No CAD (n = 13), CAD patients with (n = 10) or without (n = 16) statin therapy. From 4 CAD patients, EPCs were tested before and after 4 weeks of therapy with 20 mg atorvastatin. After 6 days of co-culture with rat neonatal cardiomyocytes, EPC differentiation was quantified by immunostaining for alpha-sarcomeric actinin flow cytometry analysis. After 6 days of co-culture, the percentage of -sarcomeric actinin-positive EPCs was significantly (p = 0.014) higher in EPCs from adults without CAD (8.07% +/- 1.48% of EPCs) compared to EPCs from CAD patients without statin (3.56% +/- 0.72%). Importantly, patients with statin therapy revealed significantly higher numbers of alpha-sarcomeric actinin-positive EPCs (6.36% +/- 0.69%, p = 0.01) compared to CAD patients without statin. In addition, statin therapy resulted in a significant (p = 0.017) increase of EPC differentiation in all 4 CAD patients investigated before and 4 weeks after statin therapy. The survival of EPCs did not differ between the different groups suggesting that the regulation of EPC differentiation is not secondary to altered EPC survival. In vitro, EPC treatment with 0.1 micro M atorvastatin did not affect EPC differentiation (116.15% +/- 49.11% of control).EPCs from patients with CAD display impaired differentiation into cardiomyogenic cells. This defect can be improved by in vivo, statin therapy.