PURPOSE: To investigate the association between varus alignment and post-traumatic osteoarthritis (OA) after an anterior cruciate ligament (ACL) injury. METHODS: One hundred subjects with an acute complete ACL tear were followed for 15 years. Anterior-posterior radiographs of the tibiofemoral joint were obtained with a knee flexion of 20°, and the patellofemoral joint was examined with skyline view at 50° knee flexion. Joint space narrowing and osteophytes were graded in the tibiofemoral and patellofemoral joints in the injured (ACL) and uninjured knee according to the radiographic atlas of the Osteoarthritis Research Society International. The alignment of the uninjured, contralateral knee was measured at follow-up, using full-limb radiographs of leg with the knee in full extension. Alignment was expressed as the hip-knee-ankle (HKA) angle. Alignment was defined as valgus (HKA ≤178°), neutral (179°-181°) or varus (≥182°). RESULTS: Data from 68 subjects were included in the analysis. Varus alignment of the uninjured knee at follow-up appeared to be associated with OA of the injured knee 15 years after an ACL injury (odds ratio (95 % confidence interval) 3.9 (1.0-15.8, p = 0.052)). CONCLUSIONS: Varus alignment of the uninjured knee at follow-up may be associated with OA of the injured knee 15 years after an ACL injury. LEVEL OF EVIDENCE: II.