Abstract:[Objective] To compare the clinical efficacy of intramedullary nailing (IMN) versus minimally invasive percutaneous plate osteosynthesis (MIPPO) for humeral shaft fractures in the adult. [Methods] A retrospective study was done on 59 adult patients who re- ceived surgical treatment for humeral shaft fractures in our hospitals from January 1, 2016 to January 1, 2021. According to preoperative doctor- patient communication, 26 patients underwent IMN, while the remaining 33 patients had MIPPO used. The documents regarding perioperative period, follow-up and radiographs were compared between the two groups. [Results] All the patients in both groups had opera- tion performed successfully without radial nerve or musculocutaneous nerve paralysis after operation. There were no significant differences in terms of operation time, intraoperative blood loss, incision healing grade and hospital stay between the two groups (P>0.05) , however, the incision length was significantlly longer, and the number of intraoperative fluoroscopy and posteoerative drainage volume were significantly lower in MIPPO group than those in IMN group (P<0.05) . All patients in the two groups were followed up for more than 12 months. During the follow-up, revision surgery for fracture nonunion happened in 4 cases of the IMN group, while 0 case of the MIPPO group, which was statistically significant (P=0.035) . In addition, revision operation was performed for subacromial impingement in 5 cases of the IMN group, while 0 case of the MIPPO group, and the difference was statistically significant (P=0.013) . Shoulder lifting ROM and UCLA shoulder score significantly improved in both groups over time (P<0.05) . The MIPPO group proved significantly superior to the IMN group in terms of shoulder lifting ROM and UCLA shoulder score at all corresponding time points postoperatively (P<0.05) , however, there was no signifi- cant difference in elbow ROM and MEPS scores between the two groups (P>0.05) . Radiographically, there was no significant difference in fracture reduction quality after operation between the two groups (P>0.05) . However, the MIPPO group got fracture healing on images sig- nificantly earlier than the IMN group (P<0.05) . [Conclusion] In this study MIPPO achieves considerably better clinical outcome than the IMN in the treatment of adult humeral shaft fractures.