Background HMG CoA reductase inhibitors increase eNOS activity by multiple mechanisms. We previously reported that genetic overexpression of eNOS improves survival and cardiac function in congestive heart failure (CHF). Presently, we tested the hypothesis that low dose treatment with an HMG CoA reductase inhibitor exerts beneficial effects on survival and/or cardiac function in a murine model of CHF. Results Mice were subjected to permanent ligation of the left coronary artery and randomized to receive either saline vehicle or simvastatin (0.25 mg/kg) two hrs post myocardial infarction and daily (0.25 mg/kg) for 7 days followed by 21 days of administration every other day for a total duration of 28 days. Myocardial infarct size was not reduced by simvastatin therapy (p = NS between groups). Simvastatin treatment did significantly (p < 0.05) improve survival (45%) compared to vehicle treatment (25%). In addition, simvastatin treatment significantly improved (p < 0.01) left ventricular function and significantly (p < 0.01) abrogated cardiac hypertrophy and pulmonary edema compared to vehicle treatment. The protective effects of simvastatin were abrogated by delayed initiation of treatment or genetic ablation of eNOS. Conclusion Low dose simvastatin therapy significantly improves survival, cardiac function, and reduces both cardiac hypertrophy and pulmonary edema via an eNOS-dependent mechanism in a murine model of congestive heart failure.