Despite significant impact biological treatment had on prospects of patients with ulcerative colitis, there is still a substantial proportion of patients with either secondary loss of response or primary non-response to multiple drugs. Beside dose optimization and selection of drugs with different mechanism of action, combination of two different targeted molecules has been proposed in cases where inflammatory activity cannot get under control. This case series provide promising results of vedolizumab in combination with tofacitinib in treatment resistent UC patients.