Background: Vedolizumab trough serum levels have been associated with clinical and endoscopic response in patients with inflammatory bowel disease (IBD). A recent study demonstrated that higher trough levels before dose escalation are associated with favorable outcomes.Objectives: We aimed to identify whether vedolizumab trough levels predict outcome of subsequent therapy.Methods: This retrospective study included IBD patients consecutively receiving vedolizumab therapy between November 2014 and June 2021. Only patients with a loss of response (LOR) to vedolizumab and available trough drug levels prior to therapy cessation were included. Clinical and endoscopic scores were recorded at 6 and 12 months post switching therapy.Results: Overall, 86 IBD patients (51 Crohn’s disease, 35 ulcerative colitis) who discontinued vedolizumab were included; of those, 72 (83.7%) were due to LOR. Upon vedolizumab discontinuation, 66.3% of patients were switched to another biologic therapy. Trough vedolizumab levels at discontinuation due to LOR did not differ between patients with clinical response and LOR regarding subsequent therapy at 6 months [median 33.8 μg/mL (IQR 13.2–51.6) versus 31.7 μg/mL (IQR 9.1–64.8),p= 0.9] and at 12 months [median 29.6 μg/mL (IQR 14.3–51.6) versus 34.1 μg/mL (IQR 12.2–64.7),p= 0.6]. Patients progressing to subsequent surgery had numerically lower vedolizumab trough levels at LOR compared with patients who were treated with an additional medical therapy (median 14.3, IQR 4–28.2 μg/mL versus 33.5, IQR 13–51.6 μg/mL,p= 0.08).Conclusions: Vedolizumab trough levels upon LOR do not predict response to subsequent medical therapy; however, lower drug levels may suggest a more aggressive disease pattern and future need for surgery.