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. © 2006 Mosby, Inc. All rights reserved.