Objective: The aim of the study was to characterize the drug utilization and switch patterns of biological treatment of ulcerative colitis (UC) and Crohn’s disease (CD). Methods: Using Danish national registries, this nationwide study included individuals diagnosed with UC or CD, bio-naïve at the initiation of treatment with infliximab, adalimumab, vedolizumab, golimumab, or ustekinumab in 2015–2020. Hazard ratios of discontinuing the first treatment or switching to another biological treatment were explored using Cox regression. Results: Among 2995 UC patients and 3028 CD patients, infliximab was used as a first-line biologic treatment in 89% of UC patients and 85% of CD patients, followed by adalimumab with 6%, vedolizumab with 3%, and golimumab with 1% for UC, and adalimumab with 12%, vedolizumab with 2%, and ustekinumab with 0.4% for CD. When comparing adalimumab as the first treatment series to infliximab, there was a higher risk of treatment discontinuation (excluding switch) among UC patients (hazard ratio: 2.02 [95% confidence interval: 1.57; 2.60]) and CD patients (1.85 [1.52; 2.24]). When comparing vedolizumab to infliximab, there was a lower risk of discontinuation for UC patients (0.51 [0.29–0.89]), and for CD patients, although not significantly (0.58 [0.32–1.03]). We observed no significant difference in the risk of switching to another biologic treatment for any of the biologics. Conclusion: More than 85% of UC and CD patients initiating biologic therapy had infliximab as their first-line biologic treatment, in accordance with official treatment guidelines. Future studies should explore the higher incidence of treatment discontinuation of adalimumab as the first treatment series.Key summary Several biologic therapies are available in the treatment of ulcerative colitis and Crohn’s disease. Clinical guidelines stipulate that infliximab should be the first-line biologic therapy. Drug utilization studies comparing biologic therapies head-to-head are sparse. In Denmark, during 2015–2020 infliximab remained the most widely used biologic treatment, with adalimumab being second. One in four patients experienced more than one biologic during the study period. The risk of discontinuation of biologic treatment (and not starting a new biologic) was higher for initiators of adalimumab. Clinical and social background factors available from the registers could not account for the observed risk difference in discontinuation.