Osteoarthritis (OA) is the leading cause of pain and disability in the elderly with the knee being the most affected weight bearing joint. We used a musculoskeletal biomechanical model of the lower extremity including a detailed validated knee joint finite element model to compute lower extremity muscle forces and knee joint stresses-strains during the stance phase of gait. The model was driven by gait data on OA patients, and results were compared with those of the same model driven by data on normal controls. Additional analyses were performed with altered cartilage-menisci properties to evaluate the effects of deterioration during OA. In OA patients compared to normal subjects, muscle forces dropped at nearly all stance periods except mid-stance. Force in the anterior cruciate ligament remained overall the same. Total contact forces-stresses deceased by about 25%. Alterations in properties due to OA had negligible effects on muscle forces, but increased contact areas and cartilage strains and reduced contact pressures. Reductions in contact stresses and increases in tissue strains and transfer of load via menisci are partly due to the altered kinetics-kinematics of gait and partly due to deterioration in cartilage-menisci properties in OA patients. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:69–78, 2014.