OBJECTIVES: Androgen deprivation therapy (ADT) leads to loss of lean mass (LM) and reduced strength and physical function. Resistance exercise alone can counteract these changes; however, it is unknown if the addition of creatine supplementation can further protect against these ADT-induced toxicities. We compared the effects of creatine supplementation with resistance exercise versus resistance exercise alone in patients with prostate cancer undergoing ADT on LM, muscle strength, and physical function. DESIGN: A 12-week randomized trial. METHODS: Men with prostate cancer receiving ADT (n = 30) were randomized to either resistance exercise + placebo (PLA) or resistance exercise + creatine (SUPP), with both groups undertaking supervised exercise 3 days per week. Outcomes included whole body and appendicular LM and fat mass (FM) assessed by dual-energy X-ray absorptiometry, as well as muscle strength (chest press, seated low, leg press), and physical function (timed up-and-go, chair rise, 400-m walk) assessed at baseline and following the intervention. RESULTS: Patients were aged 59-84 years with a BMI of 28.6 kg·m-2. PLA completed a mean of 30 sessions (83 %) and SUPP a mean of 33 sessions (92 %). Despite similar within-group improvements (p < 0.05) in whole-body LM (PLA +0.6 kg, SUPP +1.3 kg), appendicular LM (PLA +0.5 kg, SUPP +0.6 kg), muscle strength (PLA +8.8-49.3 kg, SUPP +9.4-40.4 kg) and physical function, there were no between group differences (p = 0.078-0.951). No adverse events were reported due to creatine supplementation or resistance exercise. CONCLUSIONS: A short-term program of resistance exercise alone results in meaningful improvements in LM, muscle strength and physical function, with no additional effects of creatine supplementation.