Abstract:[Objective] To compare the clinical efficacy of interlocking intramedullary nail (IIN) versus proximal humeral internal locked system plate (PHILOS) for internal fixation of Neer 3-part or 4-part proximal humeral fractures (PHF) . [Methods] A retrospective study was conducted on 40 patients who received open reduction and internal fixation for Neer 3-part or 4-part PHF from February 2018 to May 2020. According to the results of preoperative doctor-patient communication, 20 patients had the fractures fixed with IIN, while the re- maining 20 patients were with PHILOS. The documents regarding to perioperative period, follow-up and radiographs were compared be- tween the two groups. [Results] All the patients in both groups had operation finished successfully without serious complications. The IIN group proved significantly superior to the PHILOS in terms of operation time, intraoperative blood loss, incision length and postoperative drainage volume (P<0.05) , and there were no significant differences in intraoperative fluoroscopy frequency, wound healing and hospital stay between the two groups (P>0.05) . All patients in both groups were followed up for 12~18 months, with a mean of (14.48±3.16) months. There was a statistically significant difference in the time to return to active activity between the two groups (P<0.05) , and no statistically significant difference in the time to full weight-bearing activity (P>0.05) . Compared with those 3 months after surgery, VAS score signifi- cantly decreased, whereas the forward flexion range of motion (ROM) , Neer and ASES scores significantly increased in both groups at the latest follow-up (P<0.05) . However, there were no statistically significant differences between the two groups in the VAS score, ROM, Neer and ASES scores between the two groups at any corresponding time point postoperatively (P>0.05) . Radiographically, there was no a statis- tically significant difference between the two groups in fracture reduction quality revealed by radiographs within 3 days after surgery (P> 0.05) . The INN group got fracture healing earlier than PHILOS group, but the difference was not statistically significant (P>0.05) . [Conclusion] Both the intramedullary nailing and the plate fixations do achieve satisfactory clinical results for treatment of Neer 3-part or 4-part proximal humeral fractures. By comparison, the intramedullary nail has less iatrogenic injury.