Abstract:[Objective] To compare the clinical efficacy of intramedullary nail versus locking plate in fixation of four-part proximal humeral fractures. [Methods] A retrospective study was conducted on 25 patients who had four-part proximal humeral fractures surgically treated from January 2021 to June 2023. According to the preoperative doctor-patient communication, 13 patients received intramedullary nail (the IN group), while other 12 patients underwent locking plate (the LP group). The perioperative period, follow-up and imaging data of the two groups were compared. [Results] All patients in both groups were operated on successfully, with no serious complications occurred during the operation. The IN group proved significantly superior to the LP group in terms of operation time [(89.2±9.3) min vs (120.0±12.5) min, P＜0.001], the total incision length [(7.3±1.0) cm vs 13.5±1.1) cm, P＜0.001], intraoperative blood loss [(225.2±13.6) mL vs (300.1±15.0) mL, P＜0.001], postoperative drainage [(37.3±14.9) mL vs (53.0±15.7) mL, P=0.017] and active activity time [(2.3±0.7) days vs (3.0±0.8) days, P=0.042]. All patients in both groups were followed up for more than 12 months, and the IN group resumed full weight-bearing activity significantly earlier than the LP group [(11.5±1.2) weeks vs (13.6±1.7) weeks, P=0.002]. The VAS, ASES and Constant-Murley scores, as well as shoulder flexion-elevation and abduction-elevation ROMs in both groups were significantly improved over time (P＜0.05). The IN group was significantly better than the LP group in terms of VAS score [(6.0±1.1) vs (7.5±1.2), P=0.003] 1 day after operation, ASES score [(71.1±4.5) vs (66.9± 3.6), P=0.017], Constant-Murley score [(68.4±5.2) vs (61.0±3.5), P＜0.001], forward flexion- elevation ROM [(118.9±17.5)° vs (105.2± 12.2)°, P=0.034), and the abduction-elevation ROM [(115.8±16.5)° vs (102.4±13.2)°, P=0.036] 3 months postoperatively. Regarding imaging, there was no significant difference in fracture reduction quality between the two groups (P＞0.05). At the last follow-up, the IN group had significantly greater humeral neck-shaft angle (HNSA) than the LP group [(131.9±2.3)° vs (129.6±2.9)°, P=0.038], additionally, the former got fracture healing on images significantly earlier than the latter (P＜0.005). [Conclusion] Intramedullary nail fixation of four- part proximal humerus fractures has the advantages of less surgical trauma, stable fixation, rapid fracture healing and early rehabilitation over the locking plate.