Objective: To investigate the clinical efficacy of Patient Specific Instrumentation assisted primary knee replacement for the treatment of knee osteoarthritis complicated with extra-articular deformity. Methods: From March 2013 to June 2018, PSI-assisted primary knee replacement was performed in 31 patients with knee osteoarthritis and extra-articular deformity. The full-length CT scan of the lower extremities (hip-to-ankle joint) was performed before operation. The surgical plan was designed by data reconstruction, and the osteotomy guide block was made by 3D printing which was used to assist the total knee arthroplasty one stage. The patient's mechanical axis correction of the lower limbs and the ROM, HSS scores and VAS scores of the knees before and after surgery were observed. The postoperative complications such as infection, venous thrombosis of the lower extremities and loosening of the prosthesis were recorded. Results All patients were followed up for 12 to 63 months, with an average follow-up of 37 months. In 31 patients, the average axial angle of the coronal lower extremity was 16.1±5.7 o, and the postoperative correction was 2.9±0.5 o. The knee ROM was increased from 83.2±4.1 o before surgery to 97.2±7.8 o after operation. The HSS score increased from 54.8±6.1 points before surgery to 85.3±8.9 points after surgery. The VAS score decreased from 6.8 ± 0.5 points before surgery to 2.1 ± 0.3 points after surgery. The difference was respectively statistically significant. No complications such as infection, deep vein thrombosis of the lower extremities, instability of the knee joint, and loosening of the prosthesis were observed during the follow-up. Conclusion: Knee osteoarthritis combined with extra-articular deformity, with PSI assisted by the intra-articular compensation osteotomy combined with soft tissue balance technique to complete the total knee arthroplasty, can restore the mechanical axis of the lower extremity, and obtain satisfactory postoperative results.