Upadacitinib is an oral Janus kinase inhibitor approved to treat moderate-to-severe ulcerative colitis. Studies have shown that upadacitinib is highly effective, though use has been limited in certain populations due to concerns of side effects. Outside of animal studies and rare case reports, there are little data for the safety of upadacitinib use in pregnancy. We report a case of a patient with left-sided ulcerative colitis recurrently exacerbated by pregnancies who responded to upadacitinib in her fourth pregnancy. Additional data will be helpful to establish the safety for Janus kinase inhibitors for treatment of inflammatory bowel disease patients during pregnancy.