Objective. The benefits of physical activity among persons with or at higher risk for knee osteoarthritis are well established. However, activity levels in this population are low, in part due to concern that activity will damage the knee joint. We hypothesized that sedentary and moderate-vigorous physical activity are each associated with greater risk of radiographic worsening of knee OA.Methods. In Osteoarthritis Initiative participants with or at higher risk for knee OA enrolled in an accelerometer substudy at 48 months (study baseline), physical activity was measured by a uniaxial accelerometer (ActiGraph GT1M). Radiographic progression was defined as any 48 month to 96 month worsening of Kellgren/Lawrence (K/L) grade scores. All analyses were knee-level; we used multivariable logistic regression with generalized estimating equations, adjusting for key covariates.Results. Of the 1,206 participants, 631 (52%) were female, the mean ± SD age was 64 ± 9 years, and mean ± SD body mass index (BMI) was 28 ± 5. The mean ± SD average daily sedentary activity was 602 ± 86 minutes, average daily light activity was 284 ± 75 minutes, and average daily moderate-vigorous activity was 20 ± 20 minutes. In 1,978 knees, 267 (14%) had worsening of K/L grade scores. In the multivariable model, age, sex, BMI, and pain, were associated with K/L grade worsening, but neither sedentary activity (adjusted odds ratio [OR] 0.99 [95% confidence interval (95% CI) 0.97-1.01]) nor moderate-vigorous activity (adjusted OR 1.00 [95% CI 0.91-1.09]) were associated with K/L grade worsening.Conclusion. In persons with or at higher risk for knee OA, age, sex, BMI, and pain, but not objectively mea sured average daily minutes of sedentary or moderate-vigorous activity, were associated with subsequent worsening of K/L grade. Whether findings differ in persons with more severe knee OA and/or engaged more frequently in moderatevigorous activity should be examined in future studies.