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SummaryObjectiveTo study the association between weight gain and the risk of knee replacement (KR) due to primary osteoarthritis (OA), and to evaluate whether the association differs by age.Design225,908 individuals from national health screenings with repeated measurements of height and weight were followed prospectively with respect to KR identified by linkage to the Norwegian Arthroplasty Register. Cox proportional hazard regression was used to calculate sex-specific relative risks (RR) of KR according to change in Body Mass Index (BMI) and weight, corresponding analyses were done for age categories at first screening.ResultsDuring 12 years of follow up, 1591 participants received a KR due to primary OA. Men in the highest quarter of yearly change in BMI had a RR of 1.5 (95% confidence interval (CI) 1.1–1.9) of having a KR compared to those in the lowest quarter. For women the corresponding RR was 2.4 (95% CI 2.1–2.7). Men under the age of 20 at the first screening had a 26% increased risk for KR per 5 kg weight gain, for women the corresponding increase was 43%. At older age the association became weaker, and in the oldest it was lost.ConclusionsWeight gain increases the risk for later KR both in men and women. The impact of weight gain is strongest in the young, at older age the association is weak or absent. Our study suggests that future OA may be prevented by weight control and that preventive measures should start at an early age.