Background: Treatment of prostate cancer with androgen deprivation therapy (ADT) is associated with metabolic changes that have been linked to an increase in cardiovascular risk. Methods: This randomised controlled trial investigated the effects of a 12-week lifestyle intervention that included supervised exercise training and dietary advice on markers of cardiovascular risk in 50 men on long-term ADT recruited to an on-going study investigating the effects of such a lifestyle intervention on quality of life. Participants were randomly allocated to receive the intervention or usual care. Cardiovascular outcomes included endothelial function (flow-mediated dilatation (FMD) of the brachial artery), blood pressure, body composition and serum lipids. Additional outcomes included treadmill walk time and exercise and dietary behaviours. Outcomes were assessed before randomisation (baseline), and 6, 12 and 24 weeks after randomisation. Results: At 12 weeks, the difference in mean relative FMD was 2.2% (95% confidence interval (CI) 0.1–4.3, P=0.04) with an effect size of 0.60 (95% CI <0.01–1.18) favouring the intervention group. Improvements in skeletal muscle mass, treadmill walk time and exercise behaviour also occurred in the intervention group over that duration (P<0.05). At 24 weeks, only the difference in treadmill walk time was maintained. Conclusions: This study demonstrates that lifestyle changes can improve endothelial function in men on long-term ADT for prostate cancer. The implications for cardiovascular health need further investigation in larger studies over longer duration.