OBJECTIVES: We compared the results of plate-screw fixation and intramedullary fixation with inflatable nails for the treatment of acute humeral diaphyseal fractures. METHODS: The study included 34 patients (20 females, 14 males; mean age 36.4 years; range 18 to 62 years) who were selected from patients treated with plate-screw fixation or inflatable intramedullary nails. The groups were matched for age, sex, severity of fracture, and the type of humeral fracture. Eighteen fractures were treated in each group. Classification of humeral fractures and open fractures were made according to the AO and Gustilo-Anderson systems, respectively. Functional evaluations were made at postoperative six and 12 months using Constant shoulder and Mayo elbow performance scores. All the patients were administered the Short-Form 36 (SF-36) questionnaire at 12 months. The two groups were compared with respect to operation time, perioperative need for blood transfusion, time to union, complications, and shoulder and elbow functions. RESULTS: The mean operation time was significantly shorter (25.3 min vs 66.1 min; p<0.001) and the need for blood transfusion was significantly less (p=0.001) with inflatable intramedullary nails. Constant shoulder and Mayo elbow scores did not differ significantly between the two groups. Implant failure was only encountered with plate-screw fixation in three patients. Union problems were observed in five patients (3 plate-screw, 2 intramedullary nail). Following plate-screw fixation, two patients developed superficial infection, two patients developed transient radial paralysis. CONCLUSIONS: Inflatable intramedullary nails can be used safely in the treatment of acute humeral diaphyseal fractures without increasing union problems and complications.