PURPOSE: Our practice has observed more hand surgery consultations in the context of opioid use (OU) that mirrors the growing opioid epidemic. Injection drug use has been shown to be associated with the need for greater healthcare utilization. This study aimed to quantify the national burden of upper extremity infections and outcomes with respect to opioid use. METHODS: All primary hospitalizations for upper extremity soft tissue infections (UEI) in the nationwide readmission database (2015-2019) were included. Patients were stratified by history of OU. Demographics, hospital characteristics, procedures during admission, length of stay, costs, and readmissions were compared. RESULTS: A total of 328,385 patients were identified of which 50,918 (15.5%) had a diagnosis of opiate use disorder. The OU cohort was younger (38 years vs. 53 years, P<0.001), mostly male (62% vs 59%, P<0.001), and more likely to be publicly insured (64% vs 54.8%, P<0.001). OU patients were more likely to undergo incision and drainage procedures (OR: 1.23, P<0.001), undergo more procedures overall during admission (0.18 procedures, P<0.001), have an unplanned 30-day readmission (OR: 1.33, P<0.001), longer length of stay (0.22 days, P<0.001), and incurred a higher incremental cost of admission (USD $1,435, P<0.001). CONCLUSION: Patients with history of OU are more likely to require more complex care for UEIs along with greater unplanned readmissions, thereby imposing a higher relative cost to the health system. These findings underscore the economic burden notwithstanding the often discussed increasing mortality from OU and importance of studying and promoting strategies to address the epidemic.