OBJECTIVE: In a cross sectional study, we investigated the relationships between knee pain and mechanical loading across the knee, as indicated by the external knee adduction moment (KAM) during walking in patients with symptomatic knee OA who were distinguished by different radiographic disease severities. METHODS: Data from 137 symptomatic medial knee OA patients were used. Based on Kellgren/Lawrence (K/L) grading, the patients were divided into radiographically less severe (K/L≤2, n=68) or severe (K/L>2, n=69) medial knee OA. Overall knee pain was rated on a 10cm visual analog scale, and peak KAM and KAM impulses were obtained from gait analyses. Mixed linear regression analyses were performed with KAM variables as the outcome, and pain and disease severity as independent variables, adjusting for age, gender, and walking speed. RESULTS: In adjusted analyses, less severe patients demonstrated negative relationships between pain intensities and dynamic loading. The severe patient group showed no relationship between pain intensity and peak KAM, and a positive relationship between pain intensity and KAM impulse. CONCLUSION: In radiographically less severe knee OA, the negative relationships between pain intensity and dynamic knee joint loading indicate a natural reaction to pain, which will limit the stress on the joint. In contrast, either absent or positive relationships between pain and dynamic loading in severe OA may lead to overuse and accelerated disease progression. These findings may have a large potential interest for strategies of treatment in knee OA.