Background:The risk of musculoskeletal injury with the introduction of moderate-to-vigorous exercise in sedentary adults is not well established. The purpose of this report is to examine the effect of a 12-month exercise intervention on musculoskeletal injury and bodily pain in predominately overweight, sedentary men (n = 102) and women (n = 100), ages 40 to 75 years.Methods:Participants were randomized to a moderate-to-vigorous aerobic exercise intervention (EX) (6 d/wk, 60 min/d, 60% to 85% max. heart rate) or usual lifestyle control (CON). Participants completed a self-report of musculoskeletal injury and body pain at baseline and 12-months.Results:The number of individuals reporting an injury (CON; 28% vs. EX; 28%, P = .95) did not differ by group. The most commonly injured site was lower leg/ankle/foot. The most common causes of injury were sports/physical activity, home maintenance, or “other.” In the control group, bodily pain increased over the 12 months compared with the exercise group (CON −7.9, EX −1.4, P = .05). Baseline demographics and volume of exercise were not associated with injury risk.Conclusions:Previously sedentary men and women randomized to a 12-month aerobic exercise intervention with a goal of 360 min/wk reported the same number of injuries as those in the control group and less bodily pain.