The toxicity and efficacy of dapsone given daily as Pneumocystis jiroveci (PCP) prophylaxis in hematopoietic stem cell transplant (HSCT) recipients who cannot take trimethoprim-sulfamethoxazole (TMP-SMX) have not been fully evaluated. We compared 155 HSCT recipients who received daily dapsone as second-line PCP prophylaxis with 310 matched control patients who received TMP-SMX throughout the posttransplantation course. Among patients who started dapsone before transplantation because of TMP-SMX allergy, there was no difference in the transfusion requirement after HSCT when compared with controls. Among patients who started dapsone after transplantation, increased red blood cell ( P<.0001) and platelet transfusion ( P=.003) requirements were noted compared with controls. This effect was, however, limited to patients who were receiving dapsone for reasons (mostly neutropenia) other than TMP-SMX allergy. Two of 155 patients developed PCP, compared with 0 of 310 controls ( P=.11); both patients survived. In conclusion, the efficacy of daily dapsone in preventing PCP was similar to that observed in patients able to remain on TMP-SMX prophylaxis. Dapsone did not seem to cause hematologic toxicity among TMP-SMX--allergic patients. The observed higher transfusion need in patients who received dapsone for reasons other than TMP-SMX allergy seems mostly due to an underlying condition of poor marrow reserve. Further studies are required to establish whether the drug has an etiologic role in these situations.