Abstract Background Increasing numbers of biologic agents are now available for the treatment of Crohn’s disease (CD) and ulcerative colitis (UC). Limited data are available on clinical characteristics of populations initiating these therapies and relevant holistic patient-reported outcomes (PROs) in the real-world. Methods We used data from IBD Partners from May 2014-May 2019. Individuals initiating an anti-tumor necrosis factor (anti-TNF) agent or vedolizumab (VDZ) were included. A subgroup with at least 6 months of follow-up who had baseline data within 90 days of therapy initiation were included in longitudinal analyses. We aimed to: 1) compare clinical characteristics of patients initiating each biologic therapy and 2) compare PROs at follow-up by drug class. Outcomes included Patient-Reported Outcomes Measurement Information System (PROMIS) T scores for anxiety, depression, fatigue, pain interference, and social satisfaction. We used logistic regression models controlling for prior biologic exposure, age, sex, prior hospitalization, disease duration, surgery (for CD), and baseline values of each PRO to compare PROs at follow-up by drug class. Levels of each PRO within a half standard deviation of the general population T score represented wellness. Results A total of 878 patients initiating anti-TNF (625 CD, 253 UC) and 651 initiating VDZ (415 CD, 236 UC) were included. Patients with CD initiating VDZ were more likely to be older, had longer disease duration, increased IBD-related hospitalization, more prior surgeries, and were more likely to be biologic exposed (P<0.05 for all). Patients with UC initiating VDZ were more likely to be male and biologic exposed (P<0.05 for both) (Table 1). In longitudinal analyses, a total of 198 patients on anti-TNF and 168 on VDZ were included for CD; a total of 85 on anti-TNF and 96 on VDZ were included for UC. Individuals with CD initiating VDZ had significantly greater fatigue, pain interference, and reduced social satisfaction at baseline compared with the anti-TNF population. For UC, PROs at baseline were similar across drug groups. In both CD and UC, there were no significant differences in adjusted odds of wellness for each PRO at follow-up by drug class (Table 2). Conclusions CD patients initiating VDZ in this real-world cohort had multiple factors consistent with more severe disease compared with those initiating anti-TNF. In longitudinal analyses after at least 6 months of treatment with VDZ or anti-TNF, there were no differences in wellness of PROs, such as anxiety, depression, fatigue, pain interference, or social satisfaction by drug class for CD or UC.