To investigate whether the outcomes, including union rates, complications, reoperations, blood loss, operative time, and range of motion, differed following intramedullary nailing (IMN) or open reduction internal fixation (ORIF) of two- and three-part proximal humerus fractures with or without ipsilateral shaft fractures and head-split patterns. This was a retrospective multicenter study at three community centers and one level 1 trauma center. Inclusion criteria were two- and three-part proximal humerus fracture treated with either IMN or ORIF from 2015 to 2022 with at least three months of postoperative follow-up. 228 patients. No significant differences in preoperative subject characteristics were observed. IMN was significantly more common with ipsilateral shaft fractures (p = 0.011). The number of fracture parts was significantly associated with treatment (p < 0.001). IMN had significantly less blood loss in two-part fractures (p = 0.016) and concomitant shaft fractures (p = 0.029), but operative time was not significantly less in any group. Union rates, complications, reoperation, postoperative humeral neck shaft angle, and postoperative range of motion were not significantly different. IMN and ORIF result in similar outcomes for proximal humerus fractures. Both treatments result in high union rates, the potential for near anatomic postoperative humeral neck shaft angles, and sufficient postoperative range of motion. IMN has lower blood loss than ORIF. IMN is a viable option for two-part proximal humerus fractures and may be effective in select three-part fractures as well. Concomitant humeral shaft fractures can be treated with either IMN or ORIF. Head-split patterns should be treated with ORIF.
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