Psychosocial characteristics may be associated with an increased risk of coronary heart disease (CHD). Whether hostility predicts recurrent coronary events is unknown. A total of 792 women in the Heart and Estrogen/progestin Replacement Study (HERS) were evaluated prospectively to determine the role of hostility as a risk factor for secondary CHD events (nonfatal myocardial infarction and CHD death). The mean age of study participants was 67 years, and the average length of follow-up was 4.1 years. The study was conducted between 1993 and 1998, and all study sites were in the United States. High Cook-Medley hostility scores were associated with greater body mass index (p = 0.01) and higher levels of serum triglycerides (p = 0.05), and they were inversely associated with high density lipoprotein cholesterol (p = 0.04), self-rated general health (p < 0.001), age (p = 0.05), and education (p = 0.001). Compared with women in the lowest hostility score quartile, women in the highest quartile were twice as likely to have had a myocardial infarction (relative hazard = 2.03, 95% confidence interval: 1.02, 4.01). The relation between hostility and CHD events was not mediated or confounded by the biologic, behavioral, and social risk factors studied. In this study, hostility was found to be an independent risk factor for recurrent CHD events in postmenopausal women.