BACKGROUND: During the Trial to Reduce Alloimmunization to Platelets (TRAP Trial), data were prospectively collected for 8769 PLT transfusions regarding the frequency of moderate to severe PLT transfusion reactions. STUDY DESIGN AND METHODS: At seven centers, 598 patients were randomly assigned to receive unmodified pooled random-donor PLT concentrates (PCs), UV-B-irradiated PCs, filtered PCs, or filtered random-donor apheresis PLTs. RESULTS: Moderate to severe transfusion reactions were an increase in temperature of at least 2°C, chills with rigors, extensive urticaria, dyspnea, cyanosis, or bronchospasm. These reactions occurred with 2.2 percent of the transfusions in 22 percent of the patients. Transfusion reactions were associated with WBC counts of more than 5 × 106 per transfusion (p = 0.002) and transfusions stored for more than 48 hours (p = 0.02). PLT counts before transfusion were significantly lower for transfusions associated with reactions (p = 0.005). Neither UV-B irradiation nor apheresis PLTs independently influenced reaction rates. The PLT increment at 1 hour after transfusion was lower for transfusions associated with reactions (p = 0.004), and the frequency of reactions was higher in PLT refractory patients (p < 0.001). CONCLUSIONS: The provision of either fresh and/or WBC-reduced PLTs may decrease the frequency of PLT transfusion reactions and improve PLT transfusion efficacy.