Abstract Cardiovascular disease (CVD) is the most common cause of death in patients with end-stage renal disease (ESRD). The optimal management strategy in this population is unknown. We studied 640 patients with ESRD and acute myocardial infarction during 1994 to 1995 as part of the Health Care Financing Administration's Cooperative Cardiovascular Project. The majority of patients were treated with medical therapy alone, 46 patients (7%) were treated with percutaneous transluminal coronary angioplasty (PTCA), and 29 patients (5%) underwent coronary artery bypass grafting (CABG). Patient characteristics and comorbid conditions were similar among the three groups. The overall 1-year mortality rate was 53%. Advanced age, low or high body mass index, history of peripheral vascular disease or stroke, the inability to walk independently, and several indicators of cardiac dysfunction were associated with an increased relative risk (RR) for death. Survival curves differed significantly by treatment modality, with 1-year survival rates of 45%, 54%, and 69% in the medical therapy alone, PTCA, and CABG groups, respectively ( P = 0.03). After adjustment for confounding variables, the RR for death was less (but not significantly so) in the CABG group (RR, 0.6; 95% confidence interval, 0.3 to 1.1). There are no randomized clinical trial data to guide therapy of CVD in patients with ESRD. On the basis of these and other available data, CABG may be the optimal therapy for CVD in ESRD. In light of the exceptionally poor outcomes observed for patients treated with medical therapy alone, it may be premature to dismiss PTCA as a therapeutic option in this population.