Background: Proximal humeral fractures that are treated with locked plate constructs remain susceptible to collapse into a varus position. The objectives of the present study were to examine how medial comminution affects fracture stability and to determine the effect of calcar fixation on osteosynthesis stability. Methods: Eleven matched pairs of cadaveric humeri were osteotomized to create standard three-part fractures involving the surgical neck and the greater tuberosity. Five matched pairs were randomly assigned to have the medial calcar region remain intact. Six matched pairs had removal of a 10-mm medially based wedge of bone to simulate medial comminution. All fractures were stabilized in a uniform fashion with a proximal humeral locking plate. The constructs were secured, and the superior portion of the humeral head was subjected to compressive loading to induce varus collapse. Load-to-failure and energy-to-failure values along with stiffness and displacement at the time of failure were determined. Results: Medial comminution decreased the mean load to failure by 48% (523 N) (p = 0.015) and the mean energy to failure by 44% (2009 Nmm) (p = 0.013). The use of calcar screw fixation increased the mean load to failure by 31% (219 N) (p = 0.002) and the mean energy to failure by 44% (1279 Nmm) (p = 0.006). Conclusions: Medial comminution significantly decreased the stability of proximal humeral fracture fixation constructs. Calcar restoration with screw fixation significantly improved the stability of repaired fractures in cadaveric specimens. Clinical Relevance: The data suggest that medial comminution is a predictor of poor stability of proximal humeral fractures and that stability may be improved through calcar restoration. Copyright © 2013 by the journal of bone and joint surgery, incorporated.