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Study Design: Retrospective review of prospective, multicenter and international cohort study., Objective: To describe the effect of gender on HRQoL, clinical outcomes and survival for patients with spinal metastases treated with either surgery and/or radiation., Summary of Background Data: Gender differences in health-related outcomes are demonstrated in numerous studies, with women experiencing worse outcomes and receiving lower standards of care than men, however, the influence that gender has on low health-related quality of life (HRQoL) and clinical outcomes after spine surgery remains unclear., Methods: Patient demographic data, overall survival, treatment details, perioperative complications, and HRQoL measures including EQ-5D, pain NRS, the short form 36 version 2 (SF-36v2) and the Spine Oncology Study Group Outcomes Questionnaire (SOSGOQ2.0) were reviewed. Patients were stratified by sex, and a separate sensitivity analysis that excluded gender-specific cancers (i.e., breast, prostate, etc.) was performed., Results: The study cohort included 207 female and 183 male patients, with age, smoking status, and site of primary cancer being significantly different between the two cohorts (P<0.001). Both males and females experienced significantly improved SOSGOQ2.0, EQ-5D, and pain NRS scores at all study time points from baseline (P<0.001). Upon sensitivity analysis, (gender-specific cancers removed from analysis), the significant improvement in SOSGOQ physical, mental, and social subdomains and on SF-36 domains disappeared for females. Males experienced higher rates of postoperative complications. Kaplan-Meier survival analysis of both the overall and sensitivity analysis cohorts showed females lived longer than males after treatment (P=0.001 and 0.043, respectively)., Conclusion: Both males and females experienced significantly improved HRQoL scores after treatment, but females demonstrated longer survival and a lower complication rate. This study suggests that gender may be a prognostic factor in survival and clinical outcomes for patients undergoing treatment for spine metastases and should be taken into consideration when counseling patients accordingly., Competing Interests: Conflict of Interest: The authors report no conflicts of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)