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To determine the effect of osteonecrosis (ON) on the clinical and functional outcome after open reduction and internal fixation of proximal humerus fractures.Prospective cohort study.Academic medical center.Over a 12-year period, patients were screened and identified on presentation to the emergency department or in the clinical office for inclusion in an institutional review board–approved registry. One hundred sixty-five patients with 166 proximal humerus fractures met inclusion criteria. Eight patients developed radiographic evidence of ON (4.8%).Surgical repair of proximal humerus fractures.Patients were divided into 2 cohorts; 1 cohort being those diagnosed with ON and the other cohort being those who were not. All patients were prospectively followed and assessed for clinical and functional outcomes at the latest follow-up visit (mean = 22.9 months) using the Disabilities of Arm, Shoulder and Hand survey along with ranges of motion of the injured extremity.Average postoperative forward elevation for patients with ON was worse than those without ON (P = 0.002). Additionally, there was a significant difference in Disabilities of Arm, Shoulder and Hand scores at the latest follow-up between the 2 groups (P = 0.026). There was no difference in external rotation or mean length of follow-up between the 2 groups (P > 0.05).This study demonstrates the negative effects of ON after open reduction and internal fixation of proximal humerus fractures. Those who develop ON have poorer functional and clinical outcomes as compared with patients without ON. Consequently, the development of ON can be used as a predictor of poor outcomes.Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.