Background Hemolytic reactions (HTRs) can occur from ABO-incompatible platelet transfusions. After a series of cases at our institution, a procedure to screen all plateletpheresis donors for high-titer ABO antibodies was implemented. Study design and methods Plasma samples from plateletpheresis donors were screened using pooled 0.8% A1 and 0.8% B RBC in buffered gel. Dilutions of 1 in 150, 1 in 200, and 1 in 250 were sequentially evaluated. A component testing positive for high-titer ABO antibodies is restricted to ABO-identical or group O recipients, or washed. Results At the initial dilution of 1 in 150, half of group O components were labeled as high-titer. At the current dilution of 1 in 250, 25% of group O components are labeled as high-titer. No platelet-associated HTR has been reported since screening began. Conclusion Universal screening for high-titer ABO antibodies in plateletpheresis donors can be implemented efficiently to reduce the risk of HTRs. The cutoff for classifying a unit as high-titer depends on the serologic method used, and may be customized by the individual facility. Our screening method uses one gel test per donation regardless of blood group, and a plasma dilution of 1 in 250 with pooled A1/B RBCs in buffered gel.