Background: Recently, several in vitro biomechanical studies that used dual small locking plate fixation for humeral shaft fractures have investigated. However, in vivo studies about dual plate fixation for humeral shaft fractures are limited. The purpose of our study was to report the outcomes of dual small plating for humeral shaft fractures in comparison with those of single large fragment plating. Methods: Sixty consecutive patients who underwent an open reduction internal fixation for humeral shaft fractures at our institution from September 2014 to December 2017 were included. Single 4.5-mm locking compression plate (LCP) fixation was used in the first 40 cases, and dual 3.5-mm LCP fixation was used in the final 20 consecutive cases. Data were collected to define patient characteristics, injury mechanism, clinical outcomes, time to surgery, operative time, estimated blood loss, and complications. Using simple radiography during the follow-up period (6, 12, 24, and 52 weeks after surgery), the shoulder and elbow joint ranges of motion (ROM) were also evaluated. Results: Demographic data, time to surgery, surgical time, and estimated blood loss had no significant differences between the two groups. No significant differences were observed in nonunion rate and union rate 3 months after surgery. However, two patients (5%) in the single 4.5-mm LCP fixation group showed metal failure and breakage. No significant differences were found in postoperative shoulder and elbow ROM. Three patients (7.5%) in the single plating group and one patient (5%) in the dual plating group developed radial nerve palsy after surgery. No vascular injury and deep infection were observed in either group. Conclusion: For diaphyseal humeral fractures, dual 3.5-mm LCP fixation to the humerus is a possible treatment choice. This method showed satisfactory union rate, ROM, and complication rate, without increasing surgical time, in comparison with the conventional single 4.5-mm LCP fixation.