BACKGROUND. Radiation therapy (RT), a critical component of breast-conserving therapy for breast cancer, has been associated with coronary artery disease (CAD) in numerous older studies, but the risk may be lower with modern techniques. METHODS. Observed rates of cardiac events in 828 patients treated with breast-conserving surgery and RT at the University of Michigan were compared with expected rates. Relations between potential risk factors and actuarial rates of first CAD event were analyzed. RESULTS. Observed risks of cardiac events were lower than expected. The standardized incidence ratio (SIR) of myocardial infarction (MI) was 0.44 (95% confidence interval [CI]: 0.21???0.70). The SIR of MI or CAD requiring intervention was 0.50 (95% CI: 0.27???0.68). With a median follow-up of 6.8 years, 12 (1.4%) patients had at least 1 MI on follow-up and 20 (2.4%) had at least 1 MI or CAD requiring intervention. Median age at first cardiac event was 75.9 years (range, 43.1???91.5). Median interval from RT to occurrence of the first cardiac event was 3.7 years (range, 13 days to 15.4 years). The 10-year cumulative incidence of MI was 1.2% and cumulative incidence of MI or CAD requiring intervention was 2.7%. On multivariate analysis, age, diabetes mellitus, active smoking, and laterality of RT were significant predictors of MI. Age and active smoking were significant predictors of MI or CAD requiring intervention. CONCLUSIONS. Patients in this series had lower risk of ischemic cardiac events than expected. Although small in absolute magnitude, patients radiated to the left side did have a statistically significant increased risk of MI. These findings support further investigation of techniques to minimize the long-term cardiac risks faced by breast cancer patients. Cancer 2007 ?? 2007 American Cancer Society.