Purpose Muscle weakness, low lean body mass, and poor physical performance are prevalent among adult survivors of childhood cancer (survivors). We evaluated the feasibility and effects of resistance training with and without protein supplementation on lean body mass and muscle strength among survivors. Methods This double-blind placebo-controlled trial enrolled survivors ≥18 to <45 yr old. Participants were randomized to resistance training with protein supplement (21 g whey protein per day, 90 kcal) (RT + S) or resistance training with placebo (sucrose, 90 kcal) (RT + P). Participants received educational materials, access to a local fitness center, and a tailored resistance training program with tapered supervision. Participant retention and adherence were used to evaluate feasibility. Lean body mass and muscle strength were assessed at baseline and 24 wk, using dual X-ray absorptiometry, and dynamometer testing or one-repetition maximum testing, respectively. Mean changes were compared with two-way ANOVA. Results Of 70 participants randomized, 57 completed the 24-wk intervention (24 in RT + S, 33 in RT + P). The RT + S group completed 74.8% and the RT + P group completed 67.0% of exercise sessions. Mean ± SD age for those who completed was 33.1 ± 7.0 yr, 67% were White and 47% female. There were no differences in change in lean mass (RT + S, 1.05 ± 2.34 kg; RT + P, 0.13 ± 2.19 kg; P = 0.10) or strength (grip RT + S, 1.65 ± 4.17 kg; RT + P, 1.63 ± 4.47 kg; P = 0.98; mean leg press RT + S, 58.4 ± 78.8 kg; RT + P, 51.0 ± 65.1 kg; P = 0.68) between groups. Both lean mass (P = 0.03) and strength (grip P = 0.003, leg press P < 0.001) increased over time. Conclusions Supervised resistance training among survivors with protein supplementation is feasible but not more effective at increasing total lean body mass than resistance training alone.