BACKGROUND: Case reports describe the use of oral vancomycin therapy (OVT) in adult patients with concomitant symptomatic inflammatory bowel disease (IBD) and primary sclerosing cholangitis (PSC). OVT is associated with a higher likelihood of IBD remission in pediatric IBD-PSC patients. However, there are limited data on the association between OVT and IBD disease course in adult IBD-PSC patients. METHODS: We retrospectively evaluated IBD therapy intensification in adults with IBD-PSC prescribed OVT at 2 centers. Subjects were stratified by time "on" and "off" OVT. Only those who spent a minimum of 12 months in each period were included. The primary outcome was the frequency of IBD therapy intensification events. RESULTS: Of 31 patients initially considered, 22 met the inclusion criteria. Most patients (68.2%) had fewer or no intensification events while "on OVT" compared to those "off OVT". OVT was associated with fewer therapy intensification events (1.7 vs. 6.7, P=0.021) and steroid prescriptions (0.6 vs. 3.2, P=0.013) per 10 person-years. CONCLUSIONS: OVT use is associated with less need for IBD therapy intensification in symptomatic IBD-PSC adult patients. Prospective trials of OVT in such patients are warranted.