Objective: To evaluate the mid-term clinical efficacy of plate and intramedullary nail for humeral shaft fracture. Methods: In this retrospective study a total of 122 patients with humeral shaft fracture were divided into 2 groups according to surgery type from May 2010 to July 2012. There were 63 patients in plate group and 59 patients in intramedullary nail group. The factors related to the operation for each group were compared respectively. The clinical outcome was evaluated by the Neer scores, Myao scores and EuroQol 5 dimensions scores (EQ-5D). All the patients were followed up periodically in the next 3 years. Results: There were no significant differences between the two groups on hospital stay and time of returning to work (P>0.05). While the operation time, amount of intraoperative blood loss and complication rate were less in intramedullary nail group. The mean follow-up duration was (41.2±4.2) months in plate group and (42.1±4.7) months in intramedullary nail group respectively. At the last follow-up the postoperative Neer scores, Myao scores and EQ-5D scores showed no significant differences between the 2 groups[Neer: (93.8±6.1) vs(92.1±4.2); Myao: (94.9±2.9) vs(96.2±1.5), P>0.05]. There were no cases complicated with nonunion, delayed union, infection and deformity during the follow-up period. Conclusions: The mid-term outcome of open reduction and internal fixation with plate and close reduction with intramedullary nail for humeral shaft fracture is satisfactory. Although both surgeries are safe and effective, they also have some defaults. The doctors should choose the right surgery carefully according to the actual situation of the patients.