Introduction: Risk factors associated with various adverse outcomes for patients undergoing open reduction and internal fixation (ORIF) of the ankle, and how these risks differ between younger and older patient populations, has not been clearly established. Objective quantitative data may aid physicians in surgical decision making, individualizing postoperative management, and targeting interventions for reducing postoperative comorbidity. The purpose of this study is to compare the incidence of and risk factors for adverse postoperative outcomes following ORIF of ankle fractures across patient age groups. Materials and methods: Charts of patients age 18 years and older who underwent open reduction and internal fixation (ORIF) for any closed, non-polytraumatic, non-pilon ankle fracture at a single institution between the years 2008 and 2018 were reviewed. Demographic information, comorbidities, and postoperative outcomes were collected. Relative risks for adverse outcomes were calculated and compared between patients younger than 50 and patients 50 years and older. Results: A total of 886 patients were included, 375 (42.3%) of which were over age 50. In both age groups, risk of infection was significantly increased among patients with hypertension, although risk among older patients (RR = 3.52, p = 0.004) was greater than that among younger patients (RR = 2.46, p = 0.017). In patients younger than 50, significant risk of wound dehiscence was associated with tobacco use (RR = 3.39, p = 0.022), substance use (RR = 3.07, p = 0.020), and CHF (RR = 12.77, p < 0.001). Risk of implant failure was significantly increased among younger patients with HIV (RR = 4.33, p = 0.026), CHF (RR = 10.54, p < 0.001), and CKD (RR = 10.54, p < 0.001), and among older patients with HTN (RR = 4.51, p = 0.006), CHF (RR = 5.83, p < 0.001), and tobacco use (RR = 3.82, P = 0.001). Conclusion: Patients undergoing ORIF of the ankle should be well-informed of the potential risks of surgery as they pertain to specific comorbidities. Multidisciplinary approaches are warranted for appropriate management of patients with multiple comorbidities.