OBJECTIVE: To determine whether progressive resistance training improves muscle strength, muscle endurance, and physical function in adults with Down syndrome. DESIGN: Single-blind randomized controlled trial. SETTING: General community. PARTICIPANTS: Adults (N=20) with Down syndrome (13 men, 7 women; mean age, 26.8+/-7.8 y) were randomly assigned through a concealed allocation block randomized method to either an intervention group (n=9) or a control group (n=11). INTERVENTION: The intervention was a supervised, group progressive resistance training program, consisting of 6 exercises using weight machines performed twice a week for 10 weeks. Participants completed 2 to 3 sets of between 10 to 12 repetitions of each exercise until they reached fatigue. The control group continued with their usual activities. MAIN OUTCOME MEASURES: The outcomes measured by blinded assessors were muscle strength (1-repetition maximum [1-RM]), muscle endurance (number of repetitions at 50% of 1-RM) for chest press and leg press, timed stairs test, and the grocery shelving task. RESULTS: The intervention group showed significant improvement in upper-limb muscle endurance compared with the control group (mean difference in the number of repetitions of the chest press at 50% of 1-RM was 16.7, 95% confidence interval, [CI] 7.1-26.2); and a trend toward an improvement in upper-limb muscle strength (mean difference in chest press 1-RM, 8.6 kg; 95% CI, -1.3 to 18.5 kg) and in upper-limb function (mean difference in grocery shelving task, -20.3s; 95% CI, -45.7 to 5.2s). There were no significant differences between the groups for lower-limb muscle performance or physical function measures. No major adverse events for the intervention were noted. CONCLUSIONS: Progressive resistance training is a safe and feasible fitness option that can improve upper-limb muscle endurance in adults with Down syndrome (ACTR identifier ACTRN 012606000515594.).