Objective To investigate the feasibility and effectiveness of high tibial osteotomy (HTO) in treatment of chronic multi-ligament knee injury (MLKI) associated with lower extremity malalignment. Methods A clinical data of 14 patients (14 knees) of chronic MLIK associated with lower extremity malalignment, who were treated with HTO between January 2016 and September 2020, was retrospectively analyzed. There were 10 males and 2 females, with an average age of 30.5 years (range, 22-48 years). The causes of injury included traffic accident in 8 cases, bruising by an heavy object in 3 cases, falling from height in 2 cases, and twisting in 1 case. According to Schenk classification of MLKI, there were 4 cases of KD-I, including 2 cases of anterior cruciate ligament (ACL) and posterolateral complex (PLC) injuries, and 2 cases of posterior cruciate ligament (PCL) and PLC injuries; 7 cases of KD-Ⅲ were all ACL, PCL, and PLC injuries; 3 cases of KD-Ⅳ. The preoperative hip-knee-ankle angle (HKA) was (167.1±4.7)°, and the posterior tibial slope angle (PTSA) was (16.3±2.7)°. The knee joint was severely unstable and the patients could not stand and walk normally. Among them, 5 cases of medial compartment cartilage were severely worn out (3 cases of Kellgren-Lawrence type Ⅱ, 2 cases of type Ⅲ) causing pain. After admission, 2 cases of KD-Ⅰ underwent HTO and ligament reconstruction in the first stage, 1 case of KD-Ⅲ and 1 case of KD-Ⅳ underwent HTO in the first stage and ligament reconstruction in the second stage; the remaining 10 patients only received HTO. Results All patients were followed up 12-50 months, with an average of 30 months. The incisions healed by first intention after operation, and no complications such as infection and deep vein thrombosis of the lower extremities occurred. At 6 months after operation, knee range of extension was –5°-0° (mean, –1.2°) and range of flexion was 110°-140°(mean, 125.5°). The Lachman test were negative in 11 cases and positive in 3 cases. The posterior drawer test were negative in 9 cases and positive in 5 cases. The 0/30° inversion stress test was negative in 10 cases and positive in 4 cases. The 0/30° valgus stress test was negative in 13 cases and positive in 1 case. The VAS score was significantly lower than that before operation (P<0.05), and the IKDC score, Lysholm score, and Tegner score were all significantly higher than those before operation (P<0.05). The X-ray film reexamination at 12 months after operation showed that the HKA was (178.2±3.8)° and the PTSA was (8.6±2.4)°, which were significantly different from those before operation (P<0.05). All osteotomies achieved bone union, and the healing time was 3-11 months, with an average of 6.8 months. Conclusion For chronic MLKI associated with lower extremity malalignment, HTO can restore normal lower extremity alignment and improve knee joint function, which is a feasible salvage operation.