Cardiovascular disease (CVD) is a leading cause of death among women with nonmetastatic breast cancer. Whether exercise is associated with reductions in CVD risk in patients with breast cancer with an elevated CVD risk phenotype is not known. Using a prospective design, women (n = 2,973; mean age, 57 years) diagnosed with nonmetastatic breast cancer participating in two registry-based, regional cohort studies, completed a questionnaire that assessed leisure-time recreational physical activity (metabolic equivalent task [MET]-h/wk). The primary end point was the first occurrence of any of the following: new diagnosis of coronary artery disease, heart failure, valve abnormality, arrhythmia, stroke, or CVD death, occurring after study enrollment. Median follow-up was 8.6 years (range, 0.2 to 14.8 years). In multivariable analysis, the incidence of cardiovascular events decreased across increasing total MET-h/wk categories (Ptrend < .001). Compared with < 2 MET-h/wk, the adjusted hazard ratio was 0.91 (95% CI, 0.76 to 1.09) for 2 to 10.9 MET-h/wk, 0.79 (95% CI, 0.66 to 0.96) for 11 to 24.5 MET-h/wk, and 0.65 (95% CI, 0.53 to 0.80) for ≥ 24.5 MET-h/wk. Similar trends were observed for the incidence of coronary artery disease and heart failure (P values < .05). Adherence to national exercise guidelines for adult patients with cancer (ie, ≥ 9 MET-h/wk) was associated with an adjusted 23% reduction in the risk of cardiovascular events in comparison with not meeting the guidelines (< 9 MET-h/wk; P < .001). The association with exercise did not differ according to age, CVD risk factors, menopausal status, or anticancer treatment. Exercise is associated with substantial, graded reductions in the incidence of cardiovascular events in women with nonmetastatic breast cancer.