The aging population and the associated demand for orthopedic surgeries are increasing health costs. Although the Diagnostic Related Groups (DRG) system was introduced to offer incentives for hospitals, concerns remain that reimbursements for older and frail patients do not cover all hospital expenses. We investigated further: (1) Does age influence net financial results in orthopedic surgery? (2) Are there patient or surgical factors that influence results? This retrospective, monocentric study compares costs and reimbursements for orthopedic patients in a tertiary care hospital in Switzerland between 2015 and 2017. The data of 1230 patients were analyzed. Overall, the net results for the hospital were positive, despite 19.5% of patients being treated at a loss. We did not find any correlation between age and profitability (p = 0.61). Patient-related factors associated with financial losses were female sex (p < 0.001) and diabetes (p = 0.013). Patients free of serious comorbidities (p = 0.012) or with a higher cost weight (p < 0.001) were more often profitable. A longer length of stay was associated with higher losses (p < 0.001). This is the first study to address the Swiss DRG reimbursement system in a broad orthopedic population, while also analyzing specific patient and surgical factors. Overall, the reimbursement system is fair, but could better account for certain interventions.