In organ transplantation, immunological risk assessment uses cell crossmatch (XM) results, which can be altered by several drugs. We observed two recipients awaiting kidney and liver transplantation with positive flow cytometry XM (FCXM) on T-cells in the absence of Donor Specific Antibodies (DSA). Both were treated with vedolizumab (VDZ) for an inflammatory bowel disease (IBD). VDZ is an IgG1 directed against integrin alpha4beta7, expressed on T and B cell subsets, we therefore suspected that VDZ interfered with XM. We tested with Luminex screening and single antigen assays and with auto- and allo-FCXM on different HLA-typed cells several sera from the two recipients, collected before and during treatment with VDZ. To assess the intensity and the kinetics of the interference, the sera collected during VDZ treatment were from the induction and the maintenance phases at different times post-injection. All sera were DSA-negative with Luminex assays, indicating the absence of interference of VDZ with virtual XM. IgG allo-FCXM on T cells was positive during the maintenance phase while it was randomly positive on B cells. On T cells, the ratio was between 1.6 and 4.4 times the negative control (positivity threshold of 1.5) for the two recipients, and did not depend on the time between collection and injection. Unique T cell populations express Integrin alpha4beta7, then we did not observe a global shift for T cells in the presence of VDZ but a shift for a small subset which was sufficient to induce a positive FCXM. VDZ treatment did not interfere with complement-dependent cytotoxicity XM or with IgM FCXM. Pronase treatment abrogated VDZ interference. In the event of unexpected positive FCXM on T cells in a recipient with IBD, the transplant team should seek VDZ treatment and interference.