The 20-hour posttransfusion platelet count determines transfusion policy for patients requiring platelet support, and yet factors influencing the 20-hour count have been poorly defined. The clinical factors influencing both the 1- and 20-hour corrected count increment (CCI), were studied in 623 human leukocyte antigen (HLA)-unmatched platelet transfusions in 108 patients. The 1- and 20-hour CCIs were highly correlated (r = 0.67, p less than 0.001). On average, the 20-hour CCI was 64 percent of the 1-hour CCI. Multiple linear regression analyses identified splenectomy, bone marrow transplantation, disseminated intravascular coagulation, administration of amphotericin B, palpable spleen, and HLA antibody grade as the major factors influencing the 20-hour posttransfusion CCI. Platelet-specific antibodies, number of concurrent antibiotics, clinical bleeding, and temperature did not significantly influence the 20-hour posttransfusion CCI. The 1-hour CCI was the only significant factor influencing the 20-hour CCI in a regression model containing the 1-hour CCI and the above factors. Thus, the same clinical factors exert a major influence on the CCI at both 1 and 20 hours after platelet transfusion, with no evidence that any factor has more influence at 20 hours after transfusion than at 1 hour.