Background: This study aims to assess the impact of nicotine dependence on both 90-day major postoperative outcomes and 2-year implant-related outcomes in patients undergoing open reduction internal fixation (ORIF) for distal radius fractures. Methods: We queried TriNetX, a national research database that provides real-time access to deidentified medical records, for patients of all ages who underwent an ORIF of the distal radius (Current Procedural Technology codes 25607, 25608, 25609) between 2001 and 2021. Patients were categorized by nicotine dependence history (International Classification of Diseases, Tenth Revision code: F17), with groups 1:1 propensity matched for age, sex, race, ethnicity, body mass index, type 2 diabetes, hypertension, cerebrovascular disease, and chronic obstructive pulmonary disease. The primary analysis examined major postoperative complications within 90 days, while the secondary analysis assessed hardware-related issues within 2 years. Risk ratios and 95% confidence intervals were generated for each outcome. Results: Of 62 137 patients treated with distal radius ORIF, 7764 had nicotine dependence, and 54 373 did not. Each group comprised 7591 patients after 1:1 matching. Nicotine dependence was associated with increased risk of skin infections, sepsis, and wound disruption in the 90-day postoperative period ( P < .001). Within the 2-year postoperative period, nicotine dependence was associated with increased risk of mechanical complication of internal fixation device ( P < .001), nonunion ( P < .01), and surgical intervention for nonunion ( P = .009). Conclusions: Nicotine dependence is associated with increased risk of infection, sepsis, wound disruption within 90 days, and hardware complication, nonunion, and nonunion repair at 2 years. These data emphasize the importance of nicotine counseling by treating surgeons.