Abstract Background There is evidence for an exposure-efficacy relationship for vedolizumab induction therapy in patients with inflammatory bowel disease (IBD). In contrast to anti-tumour necrosis factor agents, the correlation between the response to dose optimisation and changes in the pharmacokinetic profile of vedolizumab-treated patients remains unknown. Methods This was a retrospective analysis of all vedolizumab-treated patients that increased dosing frequency because of primary non-response or secondary loss of response in a tertiary referral IBD centre between April 1, 2016 and May 31, 2017. Treatment response, defined as an improvement in clinical symptoms and objective signs of inflammation at the end of follow-up, was correlated with early changes from baseline of vedolizumab trough concentrations after dose optimisation. Results A total number of 23 IBD patients, eight with ulcerative colitis (UC) and 15 with Crohn’s disease (CD), underwent dose optimisation of vedolizumab. The median time since the start of vedolizumab was 6 months (IQR 3–9.5 months). There were seven patients (1 UC, 6 CD) with primary non-response to vedolizumab and 16 patients (7 UC, 9 CD) with secondary loss of response to vedolizumab. After complete follow-up with a median time of 9 months (IQR 5–13 months), treatment response could be restored in 12 of 23 (52.2%) vedolizumab-treated patients (4 of 8 UC, 8 of 15 CD). Median vedolizumab trough concentration at baseline was 9.5 μg/ml (IQR 5.5–14.4 μg/ml) in patients with response to dose optimisation and 7.0 μg/ml (IQR 2.0–16.0 μg/ml) in patients without response to dose optimisation (p-value = 0.26). Mean change from baseline of vedolizumab trough concentrations at Month 3 after dose optimisation was numerically higher in the group of responders vs. the group of non-responders (22.9 μg/ml vs. 11 μg/ml; p-value = 0.07). Time point Responders (n = 12) Non-responders (n = 11) Baseline Vedolizumab TC, μg/ml, mean (SD) 11.4 (9.0) 10.5 (11.1) Month 3 Vedolizumab TC, μg/ml, mean (SD) 34.3 (21.8) 21.5 (14.9) Vedolizumab TC compared with baseline, ∆, μg/ml, mean (SD) 22.9 (19.3) 11 (7.3) Mean vedolizumab trough concentrations and change from baseline after dose optimisation in the group of responders vs. the group of non-responders (SD: standard deviation, TC: trough concentration) Conclusions Dose optimisation resulted in a treatment response in more than half of IBD patients with primary non-response or secondary loss of response to vedolizumab. Early changes in the pharmacokinetic profile of vedolizumab tended to predict response after dose optimisation at the end of follow-up.