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Abstract Background Asplenia vaccination is employed before ABO‐incompatible (ABOi) transplantation in case splenectomy is needed. Pneumococcal vaccines have been reported, in different patient groups, to increase anti‐A/B titers, through cross‐reactivity to shared polysaccharide epitopes. We investigated the impact of pretransplant asplenia vaccinations on anti‐A/B antibody titers in prospective ABOi renal transplant recipients. Methods Published asplenia vaccine microbial structures were reviewed to assess expression of A/B antigens. All patients who underwent ABOi transplantation at Monash Medical Centre with anti‐A/B titers taken either side of asplenia vaccination were included in a retrospective cohort study between 2007 and 2021. Patients with paired titers without intervening vaccination were included as controls. Paired titers were compared within groups. Results A and B antigens were found to be expressed by vaccine specific pneumococcal serotypes. Thirty‐nine ABOi renal transplant recipients received vaccination including at least one pneumococcal vaccine. The most common donor to recipient combination was A1 to O. The median pre‐ and postvaccination anti‐A/B titers were 1:32 and there was no significant change in titers following vaccination (median change in titer 0 dilutions, range –2 to 3, P = 0.43). The same findings were apparent in the control group (n = 20). There was no significant change in titer by donor blood group or vaccine type. No transplants were canceled or delayed by a rise in anti‐A/B titers postvaccination. Conclusion Pneumococcal vaccination had no clinically relevant impact on anti‐A/B titers before ABOi transplantation in this cohort. These results provide reassurance regarding the safety of asplenia vaccination before ABOi transplantation.