Invasive fungal infection is one of the major causes of death in neutropenic patients undergoing allogeneic stem cell transplantation (SCT). Although prophylactic antifungal therapy with fluconazole (FLCZ) has become the standard care for these patients, there remains a need for more effective and cost-beneficial alternative drugs. We conducted a prospective study to evaluate the usefulness of the administration of micafungin (MCFG) as a prophylactic antifungal therapy for patients undergoing allogeneic SCT. The results were compared with previous data for patients who had received FLCZ. A total of 44 patients who underwent allogeneic SCT were enrolled in the study. Data from 29 patients who received allogeneic SCT using prophylactic FLCZ before this study were used as historical control data. Underlying diseases included acute leukemia (n = 16), non-Hodgkin's lymphoma (n = 11), myelodysplastic syndrome (n = 6), and others (n = 11) in the MCFG group and acute leukemia (n = 18), chronic myelogenous leukemia (n = 6), and others (n = 5) in the FLCZ group. The median durations of administration of MCFG and FLCZ were 36 and 34 days, respectively. Prophylactic success, defined as the absence of proven, probable, and possible invasive fungal infection (IFI) until the end of prophylactic therapy was achieved in 36 (87.8%) of the 41 evaluated patients in the MCFG group and in 65.5% of the patients in the FLCZ group (P = 0.038). No patients in the MCFG group showed proven or probable IFI, whereas proven or probable IFI was observed in three patients in the FLCZ group. Four patients in the MCFG group required dose escalation due to febrile neutropenia. Although one patient in the MCFG group required the discontinuation of MCFG due to allergic skin eruption (grade 2), none of the other patients in either group required dose reduction due to adverse effects. Although the study design was not a prospective randomized trial, our results indicate that the administration of MCFG at a daily dose of 100 mg is promising for prophylactic antifungal therapy in patients undergoing allogeneic SCT.