The purpose of this study was to evaluate: (1) improvement of functional and quality of life scores, (2) adverse events, (3) short-term implants survivorship of a newly designed fixed-bearing partial knee replacement (PKR) with a morphometric tibial tray in a large and multicentric population at a minimum follow-up of 2years. From 2017 to 2019, 479 medial PKR were implanted by 16 non-developing surgeons from United States, Europe, and Japan. Eight patients were lost to follow-up (1.8%). Standardized follow-up procedures included patient-reported outcomes (Oxford Knee Society score, Forgotten Joint Score, EQ VAS, EQ 5D), patient satisfaction, radiographic assessments, adverse event at 2years. Comparisons between the preoperative and postoperative values were performed using Student t test. Kaplan-Meier survivorship analysis was performed with knee revision as the endpoint. The mean age was 65.6 ± 9.6years. Mean body mass index was 29.5 ± 5.1kg/m2. Oxford Knee Society score and Forgotten Joint Score, respectively, improved from 23.7 ± 8 and 16 ± 15.8 preoperatively to 42.4 ± 6.5 and 74 ± 24.9 at 2years (p < 0.0001). Satisfaction Score was 92.3 ± 13.4 at 2years. Ten re-operations (2.1%) were reported including seven implant removals (1.5%). No other adverse event was reported. The causes of conversion to total knee arthroplasty were: nickel allergy (n = 2), patellofemoral osteoarthritis (n = 1), pain (n = 1), deep infection (n = 3). Two re-operations were performed due to infection, and one for internal fixation for a tibial plateau fracture. The 2-year Kaplan-Meier survival estimate was 98.4%, with implant removals as the endpoint. This prospective multicentric study reported safe and reliable clinical outcomes of a morphometric PKR, which optimized tibial coverage and femoral fit, in a large population of patients worldwide at 2years. Prospective cohort study-therapeutic study, Level II.