Background: Treatment of metastatic lesions to the humerus is dependent on patient's pain, lesion size and location, and post-operative functional goals. Surgical options include plate or nail fixation [open reduction internal fixation (ORIF)], or endoprosthetic replacement (EPR), with cement augmentation. The objective of this study was to perform a single institution retrospective analysis of outcomes by method of reconstruction, tumor volume, and pathologic diagnosis., Methods: The records of 229 consecutive patients treated surgically for appendicular metastatic disease from 2005-2018 at our musculoskeletal oncology center were retrospectively reviewed following institutional review board (IRB) approval. Indications for surgical treatment at the humerus included patients who presented with impending and displaced pathologic fractures., Results: Sixty patients (34 male, 26 female) with a mean age of 62.9±12.2 were identified who were treated surgically at the proximal (n=21), diaphyseal (n=29), or distal (n=10) humerus. Forty-nine (82%) patients presented with displaced pathologic fractures. The remaining eleven patients had a mean Mirels score of 9.5. There was no difference in overall complication rate between EPR or ORIF [4/36 (11%) versus 2/24 (8%); P=0.725]. Mean Musculoskeletal Tumor Society (MSTS) scores were 83% for both EPR and ORIF, with no differences in subgroup analyses at the proximal, diaphyseal, or distal humerus. Patients with cortical destruction on anterior posterior (AP) and lateral imaging were at increased risk for mechanical failure [2/6 (33%) versus 0/18 (0%), P=0.015]., Conclusions: In conclusion, when pathologic pattern permits, cement-augmented fixation allows for stabilization of pathologic bone, while minimizing risk of soft-tissue detachment, while EPR resulted in similar outcomes in patients with more extensive bone destruction. Increased tumor volume was associated with lower MSTS scores., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://aoj.amegroups.com/article/view/10.21037/aoj-20-114/coif). The series “Bone Metastasis” was commissioned by the editorial office without any funding or sponsorship. JB is a consultant and invited speaker for Merete. The authors have no other conflicts of interest to declare., (2022 Annals of Joint. All rights reserved.)