As metabolic syndrome (MetS) and a sedentary lifestyle have been associated with an increased risk of developing both prostate cancer (PCa) and cardiovascular diseases (CVDs), the 2 conditions may share a common etiology. We aimed at investigating the association between CVDs and PCa. A retrospective analysis was performed. Our dataset on patients undergone systematic prostate biopsy was searched for histopathologic and clinical data. The physical activity (PA) scale for the elderly (PASE) was collected. Coronary heart diseases (CHDs) were recorded. Prognostic Grade Group ≥3 tumors were defined as high-grade (HG). The association between MetS, PA, CHDs and PCa was assessed using logistic regression analyses. Data on 955 patients were collected; 209 (22%) presented with MetS, 79 (8%) with CHDs. PCa was diagnosed in 395 (41.3%) men and 60% (n = 238) presented with an high-grade tumor. CHDs were more common among PCa-patients (9.4% vs. 7.5%; p = 0.302) but the difference was not statistically significant. No difference was observed between low- and high-grade subgroups (9.5% vs. 9.2%; p = 0.874). PASE independently predicted PCa diagnosis (OR: 0.287; p = 0.001) and HG-PCa (OR: 0.165; p = 0.001). MetS was an independent predictor of HG-PCa only (OR: 1.50; 95% CI: 1.100–2.560; p = 0.023). CHDs were not associated with tumor diagnosis and aggressiveness.