Background: Large racial disparities persist in prostate cancer (PCa) incidence and mortality in the US. Among all races, Black men have the highest rates of PCa incidence and mortality, where they are 1.7 and 2.1 times more likely to develop and die of PCa compared to non-Hispanic White men, respectively. Androgen deprivation therapy (ADT) is one of the most recommended treatments for intermediate and advanced PCa. However, men receiving ADT have a higher risk of developing cardiovascular disease (CVD) by 65% compared to patients not receiving ADT, which is likely linked to ADT-induced cardiovascular and metabolic toxicity. Moreover, Black men with PCa receiving ADT have a higher risk of CVD-related death and a higher prevalence of comorbid conditions. Therefore, prevention and management of CVD risk factors in this population is an important unmet clinical need. Exercise is an effective way to lower CVD risk factors in many clinical settings; however, Black men with cancer are underrepresented in exercise oncology research, and no studies to date have focused on Black men with PCa on ADT. We designed a randomized controlled trial, entitled “Exercise to Enhance Cardiovascular Health among Black Prostate Cancer Patients with Androgen Deprivation Therapy: POWER Trial.” The objective of the POWER Trial is to examine the effects of a tailored exercise intervention on CVD risk factors in Black men with PCa undergoing ADT. Methods: The POWER trial is a two-arm, multi-center, randomized controlled trial, recruiting 62 Black men with localized or metastatic PCa who are receiving ADT at Dana-Farber Cancer Institute or Beth Israel Deaconess Medical Center, Boston, MA. Participants are randomly assigned to either exercise training or usual care at a 1:1 ratio. Participants in the intervention group are asked to complete a culturally tailored, home-based, virtually supervised exercise training program thrice weekly for 16 weeks. Aerobic exercise is high-intensity interval training and performed on a stationary bike, alternating 1-min high-intensity (75-95% of VO_2peak) and 1-min recovery (40% of VO_2peak) intervals. Resistance exercises are performed on large muscle groups using dumbbells with 2-3 sets of 15-20 repetitions at 60-75% of the 1-repetition maximum. Participants in the usual care group are asked not to change their baseline exercise behavior and then may cross over to the exercise program after the initial 16 weeks. The primary outcome is the CVD risk assessed by the Framingham Risk Score (i.e., age, sex, blood cholesterol, blood pressure, and smoking). The secondary and exploratory outcomes include cardiorespiratory fitness, muscular strength, body composition, patient-reported outcomes, and treatment-related symptoms. To date, five out of the planned 62 patients have been enrolled. This trial is registered in clinicaltrials.gov (NCT05327465). Clinical trial information: NCT05327465.