Anxiety and mood disorders (AMDs) are common among persons with inflammatory bowel diseases (IBD) and are associated with increased health care use and lower quality of life. We assessed the effects of AMDs on persistence on anti-tumor necrosis factor (anti-TNF) therapy in patients with IBD, and risk of IBD-related adverse outcomes after therapy initiation.We identified all persons with IBD in Manitoba, Canada who were dispensed an anti-TNF agent from 2001 through 2016 and then identified those with a validated administrative definition of AMD in the 2 years before initiation of therapy. Survival analysis was used to assess the association between active AMDs and anti-TNF discontinuation and the first occurrence of an IBD-related adverse outcome (defined as IBD-related hospitalization or surgery, new or recurrent corticosteroid use, switching to an alternative anti-TNF, or death). We used Cox proportional hazards multivariable regression models to adjust for demographic and clinical factors associated with outcomes.We identified 1135 persons with IBD who began anti-TNF therapy; 178 of these patients (15.7%) met the diagnostic criteria for an AMD. AMDs significantly increased risk of discontinuation of anti-TNF therapy (adjusted hazard ratio, 1.28; 95% CI, 1.03-1.59) and discontinuation in the 1 year following anti-TNF initiation (hazard ratio, 1.50; 95% CI, 1.15-1.94). There was no association between AMDs and subsequent risk of IBD-related adverse events.Patients with IBD and an AMD within 2 years before starting anti-TNF therapy are at increased risk of discontinuing therapy, compared to patients with IBD without AMD. Studies are needed to determine if treatment of AMDs increases compliance with treatment.