Background Patients with myocardial infarction (MI) are at further increased risk for untoward events when patients also exhibit low social support and/or depression. The ENRICHD study was the largest controlled trial in post-MI patients attempting to treat these psychological comorbidities and provides an opportunity to examine the medical and psychological characteristics that may affect risk in this population. Methods We analyzed the baseline characteristics and their relationship to the primary end point of long-term mortality and recurrent infarction and to the secondary end points of overall mortality and cardiovascular mortality in 2481 post-MI patients. Cox proportional hazards models were used to predict the risk of these outcomes over a mean of 2.5 years of follow-up. Results Death or nonfatal MI occurred in 24.1%, all-cause mortality in 13.7%, and cardiovascular mortality in 8.4% of the sample (62% of the total). Age, heart failure, pulmonary disease, Killip class, ejection fraction, an elevated creatinine, the use of non–angiotensin-coverting enzyme asodilators, prior MI, diabetes, depression, and bypass surgery after acute MI were all significant multivariable predictors. Conclusions The medical predictors of adverse events in post-MI patients with low social support and/or depression were similar to those of patients with MI in other clinical trials.