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Background: Antibiotic usage in early life has been proposed as a risk factor for inflammatory bowel disease, especially Crohn's disease. However, most studies were conducted in Western countries., Aims: We evaluated the association between antibiotic usage and the incidence of inflammatory bowel disease in the Asian population., Methods: This nationwide population-based retrospective cohort study included 2,941,889 South Korean infants born between 2007 and 2015, using the National Health Insurance Service database. We assessed whether antibiotic use was associated with the incidence of inflammatory bowel disease. Additionally, we conducted sensitivity analyses, considering protopathic bias and dietary variables. The Cox proportional hazards model was used., Results: Among 2,941,889 infants, 2,566,390 (87 %) used antibiotics within a year after birth. Antibiotic usage within a year, number of antibiotic classes, and cumulative days of usage were shown to decrease the risk of ulcerative colitis. This association was particularly prominent with earlier antibiotic exposure. Penicillin was the only antibiotic class related to the reduced risk. The results were robust after adjusting for dietary variables and considering protopathic effect., Conclusions: Antibiotic exposure during the first year of life, particularly at a younger age, is linked to a reduced risk of early-onset ulcerative colitis in South Korea., Competing Interests: Conflicts of interest There are no conflicts of interest to declare for all authors., (Copyright © 2024 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)