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Background The etiology of inflammatory bowel disease (IBD) is multifactorial and thought to be influenced by inappropriate activation of the gut mucosal immune system. As the only immunoglobulin G (IgG) subclass unable to activate the classical complement cascade, the role of IgG4 in IBD pathophysiology as an immunomodulator is controversial. This study aimed to determine the association of low, normal and high IgG4 levels with the outcomes of IBD patients. Methods This was a retrospective study of a multisite tertiary care center database evaluating patients with IBD who had an IgG4 level drawn between 2014 and 2021. Subjects were divided into low, normal, and high IgG4 level groups for evaluation of demographic and clinical indicators of IBD activity and severity. Results Of 284 patients with IBD, 22 had low (7.7%), 16 high (5.6%), and 246 (86.6%) normal IgG4 levels. There was no difference in IBD subtype, mean age, age at IBD diagnosis, or smoking between the 3 groups. There was no difference in number of hospitalizations (P=0.20), C-reactive protein levels, need for intestinal resection (P=0.85), or presence of primary sclerosing cholangitis (P=0.15), pancreatitis (P=0.70), or perianal disease (P=0.68) between the groups. Significantly more patients in the low IgG4 group had previous exposure to vedolizumab compared to the other groups and more patients in the low IgG4 group received vedolizumab (P=0.04), azathioprine (P=0.04) and prednisone (P=0.03) during the 5-year follow up. Conclusion In this study, a low serum IgG4 level was associated with higher rates of vedolizumab, azathioprine, and steroid use. [ABSTRACT FROM AUTHOR]