Inflammatory bowel disease (IBD) is a global healthcare problem that affects around 3 million people in the United States. Although the impact of gender-affirming hormone therapy (GAHT) on IBD severity has been studied in cisgender patients, there is currently no literature on the impact of exogenous hormone therapy (HT) in transgender and nonbinary (TGNB) individuals. We conducted a retrospective chart review of TGNB adults diagnosed with IBD and treated with HT for gender dysphoria at Johns Hopkins Hospital (2015-2022). We aimed to determine whether the use of GAHT was associated with subsequent increase in IBD severity. We compared the incidence of flares before vs after GAHT. Twenty-two patients were analyzed. More than half (59%) of them were assigned female at birth, identified as transmen, and underwent masculinizing HT. Their median (interquartile range) age was 30 (25-36) years. More patients had Crohn's disease compared with ulcerative colitis (13 [59.1%] vs 9 [40.9%], P = .23) with a median IBD duration of 6.2 (1.8-12.3) years. Nine (41%) patients were on biologics. Of 15 patients on HT, 8 (36.3%) experienced at least one flare. Most of them were treated with steroids (66.7%), and 6 (40%) required hospital or emergency room admission. The proportion of patients who flared after GAHT was similar to that before GAHT: 9 (60%) vs 8 (53.3%), P = 1.0. GAHT was not associated with increased incidence of flares. Larger prospective randomized studies are needed to confirm our findings and understand the interaction between GAHT and IBD in TGNB individuals.