Infections contribute significantly to morbidity and mortality after myeloablative allogeneic hematopoietic stem cell transplantation (HSCT). Whether recipients of nonmyeloablative HSCT have different posttransplantation infection risk was unknown. We therefore analyzed the incidence and risk of bacteremia during the first 100 days and of fungal infection during the first 365 days posttransplantation for 56 consecutive patients with hematological malignant disease who received nonmyeloablative HSCT (case patients). We compared the results with those among 112 control patients who received conventional myeloablative HSCT during the same years (January 1997-April 2000). Control patients were matched (2:1) for cytomegalovirus (CMV) risk group, HSC source, donor type, age, and underlying disease. Most donors (93%) were HLA-matched and related. Case patients had shorter periods of neutropenia (absolute neutrophil count, <100/mm3) than did control patients (median, 0 days; range, 0-11 versus 9 days; range, 4-25; P < .0001). This finding was associated with fewer episodes of bacteremia during the first 30 days (9% versus 27%; P = .01) and a trend to fewer episodes of bacteremia during the first 100 days posttransplantation (27% versus 41%, P = .07). Overall survival was significantly improved in case patients compared with control patients (day 100, 93% versus 81%; P = .04). During the first year posttransplantation, invasive aspergillosis occurred at a similar rate (case patients, 15%; control patients, 9%; P value not significant). Multivariate risk factor analyses identified neutropenia and CMV disease as the major factors associated with bacteremia and aspergillosis, respectively. We conclude that shorter periods of severe neutropenia in nonmyeloablative HSCT are associated with decreased risk of early bacteremia, although risk of fungal infection late after HSCT persists. This risk is an important consideration for the future development of preventive strategies.