Background: The aim of this study was to assess the clinical outcomes after treatment of proximal humeral fractures with locking plates, and to determine which factors influence the clinical and radiological outcomes. Methods: Fifty six patients who were treated with locking plates for proximal humeral fractures and had been followed for more than 1 year were enrolled in this study. We performed functional evaluation using the Constant score and analyzed radiographic results. The following factors that may potentially influence the clinical outcomes were assessed: age, gender, type of fracture, presence of medial metaphyseal comminution, bone mineral density, anatomical reduction, restoration of medial mechanical support, and postoperative complications. Results: The mean Constant score was 70.1 points at the final follow-up. Female gender, 4-part fractures, AO type-C fractures, and fractures with medial metaphyseal comminution were associated with a poor clinical outcome. On the other hand, restoration of medial mechanical support and accurate anatomical reduction had a positive influence on clinical outcomes. Postoperative complications resulted in 3 patients (intra-articular screw perforation: 1 patient, varus deformity with screw loosening: 1 patient, nonunion: 1 patient). Conclusions: When treating proximal humeral fractures with locking plate fixation, following factors: a female gender, Neer type 4-part fracture, AO type C fracture, and medial metaphyseal comminution are important risk factors that surgeons should take into consideration. Factors that contribute to better clinical outcomes of operative treatment for humeral fractures are accurate anatomical reduction and restoration of medial mechanical support.