BACKGROUND AND AIMS: 'Gut-specific' biologics are associated with fewer infectious complications than 'systemic' biologics in inflammatory bowel disease (IBD) which represents an important consideration in transplant recipients. This study evaluated the safety of combining transplant immunosuppression with 'gut-specific' versus 'systemic' biologics to manage IBD following liver transplantation (LTx). METHODS: A retrospective dual-centre study of IBD patients exposed to biologics following LTx between 2001 and 2023 was undertaken. Primary outcome was the incidence rate of infectious events per patient-year of biologic exposure. Infectious events were stratified by 'gut-specific' (vedolizumab) and 'systemic' (anti-TNF/ustekinumab) biologic exposure with severe events defined by hospitalisation. Secondary outcomes included the impact of non-biologic immunosuppression on the incidence of infectious and non-infectious complications. RESULTS: Thirty-six IBD patients were exposed to 59 (median 12 [IQR 6-27] months) biologic episodes following LTx. Patients were collectively exposed to 44.5 and 44.4 patient-years of 'gut-specific' (vedolizumab = 27 [45.7%]) and 'systemic' (anti-TNF = 22 [37.2%]; ustekinumab = 10 [16.9%]) biologics, respectively. Twenty-seven (45.7%) biologic episodes were associated with 41 infectious events, a median of 8 months (IQR 4.5-13.5) following biologic initiation. Rates of infectious events were not significantly different between 'gut-specific' and 'systemic' biologic exposures (0.43 vs. 0.50 per patient-year, incidence rate ratio [IRR] 1.09 [95% CI 0.58-2.02, p = 0.79]). Corticosteroid exposure at biologic initiation was the only non-biologic immunosuppressant associated with severe infectious events (IRR 5.40 [95% CI 1.66-17.63, p < 0.01]). CONCLUSION: Incidence of infectious events observed between IBD/LTx patients exposed to 'gut-specific' and 'systemic' biologics were similar. Biologic choice should not be influenced by concerns regarding their co-prescription with transplant immunosuppression. Corticosteroid co-therapy at biologic initiation may be associated with more severe infectious events.