BACKGROUND: The association between knee alignment and knee pain in knee osteoarthritis (OA) is unclear. High tibial osteotomy, a treatment option in knee OA, alters load from the affected to the unaffected compartment of the knee by correcting malalignment. This surgical procedure thus offers the possibility to study the cross-sectional and longitudinal association of alignment to pain. The aims were to study 1) the preoperative association of knee alignment to preoperative knee pain and 2) the association of change in knee alignment with surgery to change in knee pain over time in patients operated on for knee OA by high tibial osteotomy. METHODS: 182 patients (68% men) mean age 53 years (34 - 69) with varus alignment having tibial osteotomy by the hemicallotasis technique for medial knee OA were consecutively included. Knee alignment was assessed by the Hip-Knee-Ankle (HKA) angle from radiographs including the hip and ankle joints. Knee pain was measured by the subscale pain (0 - 100, worst to best scale) of the Knee injury and Osteoarthritis Outcome Score (KOOS) preoperatively and at one year follow-up. To estimate the association between knee alignment and knee pain multivariate regression analyses were used. RESULTS: Mean preoperative varus alignment was 170 degrees (153 - 178) and mean preoperative KOOS pain was 42 points (3 - 86). There was no association between preoperative varus alignment and preoperative KOOS pain, crude analysis 0.02 points (95% CI -0.6 - 0.7) change in pain with every degree of HKA angle, adjusted analysis 0.3 points (95% CI -1.3 - 0.6).The mean postoperative knee alignment was 184 degrees (171 - 185). The mean change in knee alignment was 13 degrees (0 - 30). The mean change in KOOS pain was 32 (-16 - 83). There was neither any association between change in knee alignment and change in KOOS pain over time, crude analysis 0.3 point (95% CI -0.6 - 1.2), adjusted analysis 0.4 points (95% CI 0.6 - 1.4). CONCLUSION: We found no association between knee alignment and knee pain in patients with knee OA indicating that alignment and pain are separate entities, and that the degree of preoperative malalignment is not a predictor of knee pain after high tibial osteotomy.