Purpose: To 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-third segment humeral shaft fractures.Methods: From November 2016 to March 2020, 14 patients (8 males and 6 females) with middle and distal-third segment humeral shaft fracture who were treated surgically by one surgeon of our department were retrospectively evaluated. Four fractures were type A1, tow fractures type A2, four fractures type A3 and four fractures type B1. In the surgical procedure, 11 fractures were treated with anterolateral MIPO approach, while three fractures used the anterolateral + lateral MIPO approach. Patient’s age averaged 48 years (range, 25–81). Results: Average follow-up time, months: 21.7, (range 12 to 36 months). QuickDASH score at final follow-up averaged 2.5 points (range, 0–4.5), The constant score averaged 88.5 points (range, 80–100). All fractures there were no nerve injuries, infections, and Other severe complications occurred.Conclusion: The 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. Our study provided a new approach for the treatment of middle and distal-third segment Humeral shaft fractures.