Earlier invasive fungal infections (IFI) put recipients of hematopoietic SCT (HSCT) at a high risk of IFI-related mortality. We retrospectively assessed the feasibility of HSCT for patients with a history of IFI and the efficacy of secondary prophylaxis. From January 2001 to December 2007, 49 patients with a history of IFI underwent HSCT and most of them received broad-spectrum antifungal agents as secondary prophylaxis. After a median follow-up of 355 days (15-967), nine patients experienced failure of IFI prophylaxis, including three cases of IFI-related death, leading to a 2-year cumulative incidence of 18.4 and 6.1%, respectively. Four risk factors for the failure of prophylaxis were found, namely time interval from the diagnosis of IFI to transplantation, residual diseases before transplantation, infection with CMV and use of corticosteroid for the treatment of GVHD. A similar outcome can be achieved in recipients of Auto- and Auto-HSCT. Despite a higher risk of post-transplant progression, residual features of IFI did not affect the overall outcome of HSCT. In conclusion, a history of IFI and residual features are not contraindications to HSCT and secondary prophylaxis by broad-spectrum antifungal agents can protect patients from relapse or progression of an earlier infection.