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Objective: The incidence and association between appendicitis and barium examination (BE) remain unclear. Such potential risk may be omitted. We conducted a longitudinal, nationwide, population-based cohort study to investigate the association between BE and appendicitis risk.Methods: From the Taiwan National Health Insurance Research Database, a total of 24,885 patients who underwent BE between January 1, 2000 and December 31, 2010 were enrolled in a BE cohort; an additional 98,384 subjects without BE exposure were selected as a non-BE cohort, matched by age, sex, and index date. The cumulative incidences of subsequent appendicitis in the BE and non-BE cohorts were assessed using the Kaplan-Meier curves and log-rank test. Cox proportional hazards regression analyses were employed to calculate the appendicitis risk between the groups.Results: The cumulative incidence of appendicitis was higher in the BE cohort than in the non-BE cohort (P = .001). The overall incidence rates of appendicitis for the BE and non-BE cohorts were 1.19 and 0.80 per 1000 person-years, respectively. After adjustment for sex, age, and comorbidities, the risk of appendicitis was higher in the BE cohort (adjusted hazard ratio = 1.46, 95% confidence interval = 1.23-1.73) compared with the non-BE cohort, especially in the first 2 months (adjusted hazard ratio = 9.72, 95% confidence interval = 4.65-20.3).Conclusions: BE was associated with an increased, time-dependent appendicitis risk. Clinicians should be aware of this potential risk to avoid delayed diagnoses. [ABSTRACT FROM AUTHOR]