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Background This cost analysis uses data from a randomized trial comparing a no prophylaxis versus prophylactic platelet ( PLT) transfusion policy (counts <10 × 109/L) in adult patients with hematologic malignancies. Results are presented for all patients and separately for autologous hematopoietic stem cell transplantation (HSCT) (auto HSCT) and chemotherapy/allogeneic HSCT (chemo/allo HSCT) patients. Study Design and Methods Data were collected to 30 days on PLT and red blood cell ( RBC) transfusions, major bleeds, serious adverse events, critical care, and hematology ward stay. Data were costed using 2011 to 2012 UK unit costs and converted into US$. Sensitivity analyses were performed on uncertain cost variables. Results Across the whole trial no prophylaxis saved costs compared to prophylaxis: −$1760 per patient (95% confidence interval [ CI], −$3250 to −$249; p < 0.05). For auto HSCT patients there was no cost difference between arms: −$110 per patient (95% CI, −$1648 to $1565; p = 0.89). For chemo/allo HSCT patients no prophylaxis cost significantly less than prophylaxis: −$5686 per patient (95% CI, −$8580 to −$2853; p < 0.01). The cost impact of no prophylaxis differed significantly between subgroups. Sensitivity analyses varying daily treatment costs and ward stay for chemo/allo HSCT patients reduced cost differences to −$941 per patient (p = 0.21) across the whole trial and −$2927 per patient (p < 0.05) in chemo/allo HSCT subgroup. Conclusions It is unclear whether a no-prophylaxis policy saves costs overall. In chemo/allo HSCT patients cost savings are apparent but their magnitude is sensitive to a number of variables and must be considered alongside clinical data showing increased bleeding rates. In auto HSCT patients savings generated through lower PLT use in no-prophylaxis arm were offset by cost increases elsewhere, for example, additional RBC transfusions. Cost-effectiveness analyses of alternative PLT transfusion policies simultaneously considering costs and patient-reported outcomes are warranted. [ABSTRACT FROM AUTHOR]