PURPOSE To estimate the risk of cardiac injury/death associated with modern radiation in a population of women with different cardiovascular (CV) risk. PATIENTS AND METHODS The data used for this analysis are from the linked SEER-Medicare database. The study included women aged 66 years and older with stage 0 - III breast cancer diagnosed between 2000 and 2005. Women were retrospectively categorized into low, intermediate, or high risk groups based on the presence of certain clinical diagnosis. The risk for a hospitalization for a cardiac event/death was estimated using a multivariable Cox model. RESULTS The median follow-up time was 24 months. Among the 91,612 women with AJCC stage 0 - III breast cancer: 39,555 (43.2%) were treated with radiation therapy and 52,057 (56.8%) were not. Radiation-treated women were younger, were likely to have pre-existing cardiovascular disease, cardiovascular risk factors and more advanced stage at diagnosis (P < .001). The following baseline characteristics were significant predictors of an increased risk for the combined outcome: decreasing year of diagnosis, age at diagnosis, AJCC stage I - III, the number of comorbid conditions, and left-sided tumor. Chemotherapy did confer an elevated risk (HRs = 1.104 - 1.282; 95% CI, 1.062 - 1.431) for the combined outcome in all three cardiovascular (CV) risk groups. The effect of radiation in the first 6 months significantly increases the risk for the combined outcome in women categorized as high risk (HR= 1.510; 95% CI, 1.396 - 1.634) for a future cardiovascular event compared to those with an intermediate risk (HR= 1.415; 95% CI, 1.188 - 1.686) or low risk (HR= 1.027; 95% CI, 0.798 - 1.321) for a future cardiovascular event. CONCLUSION The adverse cardiac effects of radiation as delivered today may pose a greater risk for an event in high risk patients and may thus require the use of techniques that further minimize the heart from radiation exposure. Recognition of the adverse cardiac effects of radiation should not offset any potential reduced risk of cancer recurrence or death from cancer, but should decrease irradiated cardiac volume as much as possible.