Abstract:[Objective] To compare the clinical outcomes of intramedullary nail versus locking plate for open reduction and internal fix- ation (ORIF) of Neer two- and three-part proximal humeral fractures. [Methods] From February 2018 to February 2021, 99 patients re- ceived ORIF for Neer two- and three- part proximal humeral fractures. According to preoperative doctor- patient communication, 57 pa- tients were treated with intramedullary nail (IMN group) , while the other 42 patients had locking plate used (LP group) . The documents re- garding to perioperative period, follow- ups and radiographs were compared between the two groups. [Results] All the patients in both groups had ORIF performed successfully. The IMN group proved significantly superior to LP group in terms of incision length, intraopera- tive blood loss, operation time and hospital stay (P<0.05) , although there was no significant difference in the incidence of early complica- tions between the two groups (P>0.05) . All patients were followed up for 14~31 months, with an average of (20.88±4.86) months. The IMN group got clinical fracture healing significantly earlier than LP group (P<0.05) . The VAS score, forward flexion and lifting range of motion (ROM) , abduction and lifting ROM, Constant-Murley score, and abductor strength were significantly improved in both groups over time (P< 0.05) , which were not statistically significant between the two groups at any corresponding time points (P>0.05) . Radiographically, there was no significant difference in fracture reduction quality between the two groups (P>0.05) , however, the IMN group achieved fracture heal- ing on images significantly earlier than LP group (P<0.05) . Compared with those preoperatively, the neck-shaft angle (NSA) of the humer- us was significantly increased in both groups postoperatively (P<0.05) , whereas which proved not statistically significant between the two groups at any matching time points (P>0.05) . [Conclusion] Both intramedullary nail and locking plate do achieve satisfactory clinical out- comes of internal fixation of Neer two- and three-part proximal humeral fractures. In comparison, intramedullary nail takes advantages of less trauma and faster fracture healing over the plate.