BACKGROUND: In infants that were exposed to biologics in utero, gastroenterology societal guidelines have either recommended against administration of the live rotavirus vaccine until 6-12 months of age or until serum biologic levels are undetectable. We performed a systematic review to evaluate the safety of rotavirus vaccination in biologic-exposed infants. METHODS: EMBASE, PubMed, Scopus, and Cochrane databases were searched from 2006 to 2024 for original data reporting on the safety of rotavirus vaccination in infants that were exposed to anti-tumor necrosis factors (TNFs) (ie, infliximab, adalimumab, golimumab, certolizumab) and non-TNF biologics (ie, vedolizumab, ustekinumab, rizankizumab, mirikizumab) in utero. RESULTS: A database search yielded 7185 screening results of which 10 studies met inclusion criteria. There were over 300 instances of rotavirus vaccination in biologic-exposed infants (n = 162 exposed to anti-TNFs, n = 142 exposed to non-TNF biologics). Biologic-exposed infants were not at an increased risk of severe adverse events or adverse events of any severity related to rotavirus vaccination. CONCLUSIONS: Administration of the live rotavirus vaccine appears to be safe in biologic-exposed infants. As such, with careful examination of the risks and benefits, there may be a role for rotavirus vaccination in this population.