Passenger lymphocyte syndrome (PLS), a subtype of graft-versus-host disease, is due to the production of antibodies by the donor "passenger" B lymphocytes against recipient's red cells. It is a rare disorder encountered mostly in ABO blood group-mismatched solid organ transplantation. The present case report illustrates the clinical presentation and the mode of management of PLS in a bidirectional ABO-incompatible renal transplantation. A 43-year-old male diagnosed with chronic kidney disease Stage 5-D (diabetic nephropathy) Type-2 hypertension with ischemic heart disease underwent ABO bidirectional-mismatched renal transplantation. The blood group of the patient was B Rh D positive and that of the donor (patient's wife) was A Rh D positive. In the pretransplantation phase, immunoglobulin G anti-A titer was 64 by column agglutination method, which was subsequently brought down to 4 by therapeutic plasma exchange and immunosuppression. Good graft function was established in the posttransplantation phase, but a significant drop in the hemoglobin (Hb) was noted. A fall in Hb, peripheral smear findings suggestive of hemolysis, and direct antiglobulin test positivity along with raised lactate dehydrogenase suggested the diagnosis of PLS; the patient was managed successfully for the same by transfusion of O blood group packed red blood cell transfusion and immunosuppression. PLS is a rare but important cause of immune-mediated hemolytic anemia in ABO-mismatched transplants.