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Background: The increased use of immunomodulators and biological agents for the treatment of patients with inflammatory bowel disease (IBD) is associated with a key safety concern considering potential opportunistic infection. Healthcare personnel were thought to be at substantial risk for acquiring such infection due to daily and close interactions with infected patients and asymptomatic carriers of pathogens.Methods: We performed a retrospective observational study, collecting data from the GETAID, between January 2015 and June 2016, on all 482 consecutive patients with IBD (68.5% with Crohn's disease, 28.4% with ulcerative colitis and 3.1% with IBD undetermined) who work as healthcare personnel (27.2% of physicians, 33.0% of nurses; 13.1% of nurses' aides and 26.7% of other healthcare personnel), in 17 tertiary centers in France and Belgium. We selected a control group of patients with IBD from the monocentric MICISTA database. Controls were matched on age (± 2.5 years), sex, IBD type and date of IBD diagnosis (± 2.5 years). Opportunistic infection was defined as (1) Clostridium difficile infection (2) community-acquired pneumonia (3) Mycobacterium tuberculosis infection (4) any community-acquired infection that required hospitalization. Opportunistic infection-free survival was studied with Kaplan-Meier method, log-rank test and Cox regression model.Results: 482 patients (126 male; median age: 24.0 [IQR 19.9–32.1] years) were included in the present study. The median follow-up period was 9.3 [4.6–16.2] years. A total of 60 opportunistic infection was recorded including 10 Clostridium difficile infection, 13 EBV or CMV-related serious viral infection, 6 tuberculosis infection including 3 tuberculosis and 3 tuberculous primo-infection, 6 community-acquired pneumonia and 5 gastrointestinal infection. The probabilities of opportunistic infection-free survival were 0.7%, 6.4%, 13.1% and 17.8% at 1, 5, 10 and 15 years. The multivariate analysis demonstrated that patients with Crohn's disease (OR=0.50, CI95% [0.30–0.83], p=0.007) were less likely to experience opportunistic infection. No difference was found between healthcare personnel and patients from the control group regarding the occurrence of opportunistic infection. Only one case of Mycobacterium tuberculosis infection was observed in the control group.Conclusions: Although there is an higher exposure to potential pathogens in healthcare personnel, this is not associated with an higher risk of opportunistic infection as compared with controls. Prospective studies are needed to confirm that the level of occupational exposure to potential pathogens should not be taken into account when discussing the introduction of immunomodulator or biological agents.