BACKGROUND Coronary artery disease (CAD) and prostate cancer (PCa) are not only common diseases, but share many risk factors. To date, only a few studies have explored the relationship between CAD and PCa risk, with conflicting results. METHODS The four-year REDUCE study tested dutasteride 0.5 mg daily for PCa risk reduction in men with prostate specific antigen (PSA) of 2.5 to 10.0 ng/mL and a negative biopsy. Among men who underwent at least one on-study biopsy (n = 6,729; 82.8%), the association between CAD and overall PCa risk and disease grade was examined with logistic and multinomial logistic regression adjusting for clinicopathologic features, respectively. RESULTS Overall, 547 men (8.6%) had a history of CAD. Men with CAD were significantly older and had higher body mass index, PSA, and larger prostate volumes and were more likely to have diabetes, hypertension, and hypercholesterolemia and take aspirin and statins. On multivariate analysis, CAD was associated with a 35% increased risk of PCa diagnosis (OR = 1.35, 95% CI: 1.08-1.67, P = 0.007), while elevating risk of both low- (OR = 1.34, 95% CI: 1.05-1.73, P = 0.02) and high-grade disease (OR = 1.34, 95% CI: 0.95-1.88, P = 0.09). CONCLUSIONS In a post hoc hypothesis developing secondary analysis of the REDUCE study, CAD was significantly associated with increased PCa diagnosis. IMPACT If confirmed in other studies, this suggests CAD may be a novel PCa risk factor and suggests common shared etiologies. Whether lifestyle changes shown to reduce CAD risk (i.e., weight loss, exercise, cholesterol reduction, etc.) can reduce PCa risk, warrants further study.