Background <p>With advances in the biocompatibility of hemodialysis membranes, severe dialyzer-associated thrombocytopenia following heparin-free hemodialysis is uncommon and is not easily detected without postdialysis regular blood tests or in the absence of postdialysis bleeding symptoms.</p> Case presentation <p>Herein, we present the case of a 58-year-old East Asian patient on hemodialysis who experienced cyclic episodes of severe thrombocytopenia following heparin-free hemodialysis, which led to significant thrombocytopenia even on nondialysis days, resulting in the cancellation of scheduled kidney transplantation. Additional tests showed no specific hematologic or other diagnosis. Hemodialysis membrane-induced thrombocytopenia was suspected because of the peridialysis pattern of the platelet count. After changing the dialyzer from a polysulfone-polyvinylpyrrolidone blend membrane to a medium cut-off polyarylethersulfone and polyvinylpyrrolidone blend membrane, the patient demonstrated considerable improvement in cyclic thrombocytopenia following hemodialysis and underwent kidney transplantation without bleeding complications. Platelet levels were fully recovered and maintained following kidney transplantation.</p> Conclusion <p>Severe hemodialysis membrane-induced thrombocytopenia following heparin-free hemodialysis can occur even in the era of dialyzers with excellent biocompatibility. Although postdialysis platelet count is not routinely measured in clinical settings, the platelet count should be determined, especially in patients with predialysis thrombocytopenia.</p>