Background: The purpose of this study was to identify demographic data, medical comorbidities, and perioperative factors that are associated with increased risk of overall surgical complications, wound complications, and reoperation within 30 days of open reduction and internal fixation (ORIF) of distal radius fractures. Methods: All adult patients undergoing ORIF of distal radius fractures in the National Surgical Quality Improvement Program database between 2005 and 2020 were identified. Patients were excluded for secondary procedures, open/infected injuries, or inpatient surgical setting. Demographic data, medical comorbidities, and perioperative data were examined for each patient, and patients were grouped by the presence or absence of any surgical complication. Univariate analysis and multivariate logistic regression were used to identify risk factors. Results: A total of 20 301 patients from between 2005 and 2020 met the inclusion criteria, of which 219 complications (1.1% of cases) were identified. Following multivariate analysis, independent risk factors found to be associated with surgical complications included male sex, smoking, heart failure, longer operative time, and American Society of Anesthesiologists (ASA) classification of 3 or higher. Conclusion: Male sex, smoking, heart failure, prolonged operative time, and ASA status of 3 or higher are associated with an increased risk of surgical complications following ORIF of distal radius fractures. These complications, with the exception of heart failure, were also associated with an increased risk of wound complications. Finally, male sex, nonwhite race, smoking, dialysis, prolonged operative time, and 3 or higher ASA class were associated with reoperations. Understanding these risk factors allows surgeons to better predict and prevent complications in high-risk populations.