Introduction Infliximab (IFX) was the first anti-tumor necrosis factor (TNFα) antibody to be used in the treatment of severe chronic inflammatory diseases, such as Crohn’s disease and rheumatoid arthritis. A number of serious adverse drug reactions are known to be associated with IFX use; they include infections, malignancies, and injection site reactions. Although a few case reports have described potential psychiatric adverse events (including suicide attempts and manic episodes), the latter are barely mentioned in IFX’s summary of product characteristics. The objective of the present retrospective study was to detect potential psychiatric adverse events associated with IFX treatment by analyzing a national discharge abstract database. Materials and Methods We performed an historical cohort study by analyzing data from the French national hospital discharge abstract database (PMSI) between 2008 and 2014. All patients admitted with one of the five diseases treated with IFX were included. Results Of the 325,319 patients included in the study, 7,600 had been treated with IFX. The proportion of hospital admissions for one or more psychiatric events was higher among IFX-exposed patients (750 out of 7,600; 9.87%) than among non-exposed patients (17,456 out of 317,719; 5.49%). After taking account of potential confounders in the cohort as a whole, a semi-parametric Cox regression analysis gave an overall hazard ratio (HR) [95% confidence interval] (CI) of 4.5 [3.95; 5.13] for a hospital admission with a psychiatric adverse event during treatment with IFX. The HR (95%CI) for a depressive disorder was 4.97 (7.35; 6.68). Even higher risks were observed for certain pairs of adverse events and underlying pathologies: psychotic disorders in patients treated for ulcerative colitis (HR = 5.43 [2.01; 14.6]), manic episodes in patients treated for severe psoriasis (HR = 12.6 [4.65; 34.2]), and suicide attempts in patients treated for rheumatoid arthritis (HR = 4.45 [1.11; 17.9]). Discussion The present retrospective, observational study confirmed that IFX treatment is associated with an elevated risk of psychiatric adverse events. Depending on the disease treated, physicians should be aware of these potential adverse events.