Abstract: Background: Polypharmacy poses a growing concern in military and veteran populations due to complex health needs arising from service-related injuries and mental health conditions. This systematic review and meta-analysis aims to synthesize existing literature on polypharmacy prevalence, focusing on both general and psychotropic medications in military and veteran populations, and to identify contributing factors. Methods: The study protocol adhered to PRISMA guidelines and was registered on PROSPERO. A comprehensive search across PubMed, Embase, Scopus, and Web of Science yielded 19 eligible studies. Two independent reviewers conducted study selection, data extraction, and quality assessment using standardized tools. The primary outcome was prevalence of polypharmacy and secondary outcomes included factors associated with increased polypharmacy risk. Results: Pooled estimates revealed a high prevalence of psychotropic polypharmacy (36 %, 95 % CI: 23–49 %) and general polypharmacy (49 %, 95 % CI: −26-72 %) among active-duty military personnel and veterans. Heterogeneity was substantial (I2 = 100 %). Subgroup analyses in studies on psychotropic polypharmacy revealed that veterans with PTSD had a higher prevalence of polypharmacy (48 %) than those without PTSD (22 %). No significant differences were found in general and psychotropic polypharmacy prevalence based on medication threshold, mean age, and geographical location. Despite heterogeneity and bias, the study indicates generally high-quality research. Conclusion: The findings emphasize the critical importance of tailored medication management strategies for military and veteran personnel, considering mental health diagnosis like PTSD. Future research should prioritize longitudinal studies to discern long-term implications and develop targeted interventions for optimizing medication use in military and veteran populations.