Objectives: To examine the relationships between weight at early and middle adulthood and adult weight gain and the risk of total knee and hip replacement for OA. Methods: At baseline interview during 1990-94, 38 149 participants [mean age 54.9 (S.D. 8.6) years] of the Melbourne Collaborative Cohort Study were asked to recall their weight at age 18-21 years and had their middle age height and weight measured. Total knee and hip replacement for OA between 2001 and 2009 was determined by linking the cohort records to the Australian Orthopaedic Association National Joint Replacement Registry. Results: Greater weight and BMI at age 18-21 years and middle age, weight gain and persistent overweight during this time were associated with an increased risk of total knee and hip replacement. Middle age weight [hazard ratio (HR) per 5 kg 1.25 (95% CI 1.23, 1.27) for knee vs 1.11 (1.09, 1.14) for hip] and BMI [HR per 5 kg/m2 1.80 (1.72, 1.89) vs 1.29 (1.21, 1.37)] and adult weight gain [HR per 5 kg 1.25 (1.23, 1.28) vs 1.10 (1.07, 1.13)] were more strongly associated with the risk of total knee replacement than total hip replacement (P for heterogeneity of HRs <0.0001). Conclusion: Greater body weight and BMI at early and middle adulthood, weight gain and persistent overweight from early to middle adulthood are risk factors for knee and hip OA. Adult weight gain confers stronger risk on knee OA than hip OA. Weight control from early adulthood and avoiding weight gain are important for the prevention of OA.