Surgical fixation of humeral shaft fractures generally involves plating or nailing. It is unclear whether one method is more effective than the other. The aim of this study was to compare the results of the intramedullary nail and locking compression plate for the treatment of humeral shaft fractures. A total of 60 patients with humeral shaft fractures were randomized to undergo surgery with an intramedullary interlocking nail (n=30) or locking compression plate (n=30). The outcome was assessed in terms of intraoperative blood loss, operative time, hospital stay, union time, union rate, functional outcome, and incidence of complications. Functional outcome was assessed using the Constant score and the American Shoulder and Elbow Surgeons (ASES) score. Intraoperative blood loss, operative time, and hospital stay in group A (intramedullary interlocking nail) were significantly lower than those in group B (locking compression plate). No statistically significant difference was found regarding the union rate, mean Constant score, and mean ASES score between the groups. The average union time was found to be significantly lower for the intramedullary interlocking nail compared with the locking compression plate. The incidence of complications such as radial nerve palsy was found to be higher with the locking compression plate compared with the intramedullary interlocking nail. The intramedullary interlocking nail can be considered a better surgical option for the management of humeral shaft fractures because it offers decreased intraoperative blood loss; shorter operative times, hospital stays, and union times; and a lower incidence of serious complications such as radial nerve palsy.