Objective To compare clinical outcomes of minimally invasive plating osteosynthesis (MIPO) and intramedullary nail stabilization in treatment of acute humeral shaft fractures. Methods From March 2007 to January 2009, 52 patients were treated in our department for acute fractures of middle and lower humeral shaft. Twenty-seven were treated with MIPO technique (group A) and 25 with intramedullary nail (group B) . In group A, there were 15 men and 12 women, aged from 18 to 65 years (average, 36. 7 years); in group B, there were 16 men and 9 women, aged from 25 to 63 years (average,39. 4 years). Operation time, amount of blood transfusion, hospital stay, time for union, complications, Mayo scores of the elbow and Constant scores of the shoulder were recorded in both groups and compared statistically. Results The mean follow-up time was 17. 8 months (range, 16 to 36 months) . There were no significant differences between the 2 groups in operation time, amount of blood transfusion, hospital stay, time for union, and Mayo scores of the elbow ( P > 0. 05) . There was no case of postoperative iatrogenic radial nerve palsy or non-union in group A, but there were 4 cases of non-union, 2 cases of iatrogenic radial nerve palsy and one case of varus malunion in group B. Compared with group B, group A showed significant advantages in rate of postoperative non-union and Constant scores of the shoulder functional recovery ( P < 0. 05) . Conclusion In treatment of humeral shaft fractures, MIPO technique has advantages of less operative invasion, quick bone union, satisfactory shoulder functional recovery and low risk of postoperative palsy of the iatrogenic radial nerve.