Abstract: OBJECTIVE: Military service is demanding and requires maintenance of optimal physical and mental health. Deployment-related incidents can precipitate the onset of physical and/or psychological trauma necessitating appropriate pharmacological intervention. However, current strategies for medical vocational rehabilitation do not include systematic medication assessment. METHODS: This study analyzed physical performance and long-term medication use in middle-aged soldiers diagnosed with physical impairments and/or posttraumatic stress disorder. Patient records were analyzed to investigate the number of drugs, polypharmacy, drug-drug interactions and drugs targeting the nervous system in relation to bicycle ergometry performance. RESULTS: A total of 172 patients were inclusion, with 45 patients (26.6%) receiving comprehensive medication. Patients with posttraumatic stress disorder, who were taking an average of 3.0 medications each, demonstrated significantly lower maximum performance than did the controls [n=93, 217 (200-250) W vs. n=34, 250 (225-267) W, P=0.006]. Polypharmacy [n=42, 217 (200-250) W vs. n=34, 250 (225-267) W, P=0.017] and drug-drug interactions [n=49, 221 (200-250) W vs. n=34, n=34, 250 (225-267) W, P=0.024] negatively impacted maximum performance, with patients experiencing 1.6 interactions on average of varying severity. A significant negative correlation was observed between the number of drugs, anatomical-therapeutic-chemical classification, polypharmacy, number, and severity of drug-drug interactions and poor maximum performance. Although no other significant differences were noted across all groups, posttraumatic stress disorder patients without medication achieved significantly greater performance than did somatic patients [n=34, 250 (225-267) vs. n=33, 217 (200-250), P=0.009]. CONCLUSION: In conclusion, highly prevalent polypharmacy may contribute to physical performance limitations, highlighting the need for further research and professional support in medication management within rehabilitation programs for mental illnesses.