Background: A recent randomized trial compared a policy of no prophylaxis with a policy of prophylactic platelet (PLT) transfusions at counts of fewer than 10?109/L in patients with hematologic malignancies. The results suggested the effectiveness of prophylactic PLT transfusions may vary according to patient diagnosis and treatment plan. Study Design and Methods: This article presents full subgroup analyses and compares treatment effects between autologous hematopoietic stem cell transplantation (autoHSCT; n=421) and chemotherapy/allogeneic HSCT (chemo/alloHSCT; n=179) patients. Results: Prespecified subgroup analysis found that the reduction in proportion of patients experiencing WHO Grade 2 to 4 bleeds (main trial outcome) seen in the prophylaxis arm was of greater magnitude in chemo/alloHSCT than autoHSCT patients (interaction p=0.04). Analysis of secondary outcomes showed a shorter time to first bleeding episode with no prophylaxis in the chemo/alloHSCT group (hazard ratio, 1.84; 95 confidence interval CI, 1.21-2.79; p=0.004) compared to the autoHSCT group (hazard ratio, 1.12; 95 CI, 0.85-1.48; p=0.4; interaction p=0.08). The increased number of days with Grade 2 to 4 bleeds with a no-prophylaxis policy was similar in chemo/alloHSCT (rate ratio, 1.89; 95 CI, 1.10-3.26) and in autoHSCT patients (rate ratio, 1.43; 95 CI, 1.04-1.97). Both subgroups showed significant reductions in PLT transfusions with a no-prophylaxis strategy. Conclusion: There is evidence that the effectiveness of prophylactic PLT transfusions may differ between subgroups, with chemo/alloHSCT patients receiving prophylactic PLT transfusions appearing to show a greater reduction in bleeding outcomes compared to patients following a no-prophylaxis policy.