OBJECTIVES: To examine whether categories of anatomic alignment (varus, neutral, valgus) measured from knee X-rays agree with similar categories of mechanical alignment from the full limb film and whether varus anatomic malalignment predicts medial joint space loss on knee X-rays as well as varus mechanical alignment. METHODS: We used data from the Osteoarthritis Initiative (OAI) (full limb and flexed knee X-rays) to examine agreement of anatomic and mechanical alignment and data from Boston Osteoarthritis of the Knee Study (BOKS) to evaluate the association of full limb mechanical alignment vs knee X-ray anatomic alignment with joint space loss. A 4 degrees offset was used to correct for the more valgus angulation of the anatomic alignment. RESULTS: Of 143 subjects whose knee X-rays and full limb films were publicly released from the OAI, the agreement of varus, neutral and valgus alignment was only moderate (kappa=0.43, P