Background: Surgery remains the best option for more advanced stages of knee osteoarthritis (OA). Kinematic alignment (KA) is an innovative surgical technique that aims to co-align the rotational axes of the femoral, tibial, and patella components with the three kinematic axes of the knee. This study aims to evaluate and analyze short-term clinical, psychological, and functional outcomes in patients undergoing total knee replacement with the KA technique. Methods: Twelve patients who underwent total knee replacement surgery with kinematic alignment from May 2022 until July 2022 were prospectively followed and interviewed. Before surgery, the day after surgery, and postoperative day 14, the following tests were evaluated: VAS, SF-12 PS, SF-12 MS, KSS, KSS-F, PHQ-9, and KOOS-PS. Results: The mean BMI value of 30.4 (±3.4) Kg/m2, mean age of 71.8 (±7.2) years. All the scores on the various tests administered consistently showed statistically significant improvement, not only immediately after surgery but also comparing the first to the fourteenth postoperative day. Conclusion: Kinematic alignment technique as a surgical treatment for KO allows the patient a fast postoperative recovery and good clinical, psychological, and functional results in a short time. Further studies are needed with a larger sample size, and prospective randomized studies are essential to compare these results with mechanical alignment.