Background: Obesity, type II Diabetes mellitus (DMII) and vascular damage could be implicated in prostate cancer (PCa) nevertheless no clear results has been reached. The aim of the research was to investigate the association of these alterations with PCa at initial diagnosis, without the influence of hormone therapy or chemotherapy. Methods: Retrospective analysis of 400 patients undergoing prostate biopsy at our institution between 2005 and 2012 was conducted. We examined associations of obesity, DMII and vascular damage in 200 patients with PCa diagnosis versus 200 age-matched controls. Men with history of hormone therapy or chemotherapy, prostate or bladder surgery were excluded. Results: Obesity was significantly associated (OR 2.10, p < 0.05) with aggressive PCa (Gleason Score 8 - 10). DMII was significantly associated to aggressive PCa but only in obese cases (OR 4.25). Carotid vascular disease (CVD) and coronary artery disease (CAD) were significantly linked to PCa in all cases versus controls (OR 1.88, p < 0.05). Conclusions: In our study, obesity, particularly in combination with DMII, was significantly associated with aggressive PCa. Moreover, a significant relation was found between vascular disease and PCa hormone-naive at initial diagnosis. The metabolic derangements associated to obesity and DMII may increase oxidative stress and cause a permanent pro-inflammatory state that predisposes to vascular disease and PCa.