The physiological role of prolactin (PRL) in men is not completely clarified. We previously reported that in subjects consulting for sexual dysfunction, lower PRL plasma levels were associated with worse lipid and glycaemic profile, as well as with a higher prevalence of metabolic syndrome and arteriogenic erectile dysfunction (ED). The aim of this study was to assess possible associations between PRL levels and incident major cardiovascular events (MACE) in subjects with ED. When only subjects without pathological hyperprolactinaemia (PRL < 735 mU/L or 35 ng/mL) and pituitary diseases were considered, both unadjusted and adjusted analyses showed a significantly lower incidence of MACE in subjects with PRL levels in the highest PRL quintile (246-735 mU/L or 12-35 ng/mL) when compared with the rest of the sample. In particular, the risk of MACE was reduced by 5% (1-9%; p = 0.03) for each 10 ng/mL increment of PRL. Conversely, comparing patients with hyperprolactinaemia with matched controls, no significant difference was detected between cases and controls in MACE. In subjects at high risk for cardiovascular diseases, such as those with ED, a relatively high PRL plasma level is associated with an overall decreased chance of MACE, independently from other known risk factors.