BackgroundTo evaluate the feasibility and safety of a new minimally-invasive surgical approach–anteromedial minimally-invasive plate osteosynthesis (MIPO)–in the treatment of middle and distal humeral shaft fractures.MethodsFourteen patients with humeral shaft fracture treated with anteromedial MIPO from November 2016 to March 2020 (MIPO Group) were selected as the study subjects. Open reduction and internal fixation (ORIF) were used to treat 14 patients with humeral shaft fractures as the control group (ORIF group). The two groups were fixed with a locking compression plate (LCP) or LCP + multi-directional locking screw system (MDLS). The incision length, intraoperative blood loss, intraoperative fluoroscopy time, operation time, length of hospital stay, fracture healing time, QuickDASH score and Constant score were observed and compared between the two groups.ResultsFourteen patients were enrolled in each group. The incision length (7.79 ± 2.39 cm), intraoperative blood loss (96.07 ± 14.96 mL), operative time (110.57 ± 21.90 min), hospital stay (6.29 ± 1.49 days) and fracture healing time (14.94 ± 0.99 weeks) in the MIPO group were all lower than those in the ORIF group, and the difference was statistically significant for each parameter (P < 0.05). The intraoperative fluoroscopy time (20.07 ± 3.22) in the MIPO group was significantly higher than that in the ORIF group (P < 0.05). There were no significant differences in age (P = 0.078), QuickDASH score (P = 0.074) or Constant score (P = 0.293) between the two groups and no postoperative complications occurred in any of the patients.ConclusionThe anteromedial approach MIPO technique has the advantages of less trauma, less bleeding, low risk of nerve injury and high rate of fracture healing. It is one of the most effective methods for the treatment of middle and middle–distal humeral shaft fractures.