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This study aimed to examine the association between objectively measured physical activity and risk of developing incident knee osteoarthritis (OA) in a community-based cohort of middle-age and older adults.We used data from the Osteoarthritis Initiative, an ongoing prospective cohort study of adults 45 to 83 yr of age at initial enrollment with elevated risk of symptomatic knee OA. Moderate–vigorous physical activity (MVPA) was measured by a uniaxial accelerometer for seven continuous days in two data collection cycles and was categorized as inactive (<10 min·wk−1), low activity (10–<150 min·wk−1), and active (≥150 min·wk−1). Incident knee OA based on radiographic and symptomatic OA and joint space narrowing were analyzed as outcomes over 4 yr of follow-up. Participants free of the outcome of interest in both knees at study baseline were included (sample sizes ranged from 694 to 1331 for different outcomes). We estimated hazard ratio (HR) with 95% confidence intervals (CI).In multivariate analyses, active MVPA participation was not significantly associated with risk of incident radiographic knee OA (HR = 1.52, 95% CI = 0.68–3.40), symptomatic knee OA (HR = 1.17, 95% CI = 0.44–3.09), or joint space narrowing (HR = 0.87, 95% CI = 0.37–2.06) when compared with inactive MVPA participation. Similar results were found for participants with low activity MVPA.MVPA was not associated with the risk of developing incident knee OA or joint space narrowing over 4 yr of follow-up among Osteoarthritis Initiative participants who are at increased risk of knee OA.