Aims: The best surgical treatment of multi-fragmentary proximal humeral fractures in the elderly is a highly controversial topic. The aim of this study is to assess for sex-related differences regarding mortality and complications after reverse total shoulder arthroplasty (RTSA) and locking plate fixation (LPF). Patients and Methods: All patients from the largest German healthcare insurance (26.5 million policy holders) above the age of 65 years that were treated with LPF or RTSA after a multi-fragmentary proximal humerus fracture between January 2010 and September 2018 were included. Multivariable Cox regression models were used to assess the association of sex with overall survival, major adverse events and surgical complications. Results: A total of 8264 (15%) men and 45,707 (85%) women were followed up for a median time of 52 months. After 8 years, male patients showed significantly higher rates for death (65.8%; 95% CI 63.9–67.5% vs. 51.1%; 95% CI 50.3–51.9%; p < 0.001) and major adverse events (75.5%; 95% CI 73.8–77.1% vs. 61.7%; 95% CI 60.9–62.5%; p < 0.001). With regard to surgical complications, after adjustment of patient risk profiles, there were no differences between females and males after LPF (p > 0.05), whereas men showed a significantly increased risk after RTSA (HR 1.86; 95% CI 1.56–2.22; p < 0.001) with more revision surgeries performed (HR 1.76, 95% CI 1.46–2.12; p < 0.001) compared to women. Conclusion: The male sex is an independent risk factor for death and major adverse events after both LPF and RTSA. An increased risk for surgical complications after RTSA suggests that male patients benefit more from LPF. Sex should be considered before making treatment decisions.