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To identify gender-specific predictors of lower extremity injury among a sample of adults engaging in running, walking, or jogging (RWJ) for exercise.Prospective cohort study.Cooper Clinic Preventive Medicine Center, Dallas, Texas.Participants were 2,481 men and 609 women who underwent a physical examination between 1970 and 1981 and returned a follow-up survey in 1986. Predictor variables measured at baseline included height, weight, and cardiorespiratory fitness. At follow-up, participants recalled information about musculoskeletal injuries, physical activity levels, and other predictors for lower extremity injury over two time periods, 5 years and 12 months.An injury was defined as any self-reported lower extremity injury that required a consultation with a physician. Cox proportional hazards regression (HR) was used to predict the probability of lower extremity injury for the 5-year recall period, and unconditional logistic regression was used for the 12-month recall period.Among men, previous lower extremity injury was the strongest predictor of lower extremity injury (HR = 1.93–2.09), regardless of recall period. Among women, RWJ mileage >20 miles/wk was the strongest predictor for the 5-year period (HR = 2.08), and previous lower extremity injury was the strongest predictor for the 12-month period (HR = 2.81).For healthy adults, walking at a brisk pace for 10–20 miles per week accumulates adequate moderate-intensity physical activity to meet national recommendations while minimizing the risk for musculoskeletal lower extremity injury. Clinicians may use this information to provide appropriate injury prevention counseling to their active patients.