Invasive aspergillosis (IA) occurs in up to 23% of allogeneic hematopoietic stem cell transplantation (HSCT) patients. Although transplant procedures have changed over time, more late cases of IA are being observed. The objective of this study was to identify the pre-and post-transplant factors of IA in a large cohort of HSCT patients mainly transplanted with reduced-intensity conditioning. This multicenter, case-control study was carried out using data collected between 2005 and 2010 by the Surveillance des Aspergilloses Invasives en France program (Institut Pasteur, Paris) and the European Society for Blood and Marrow Transplantation ProMISe registry. Four control subjects without IA were individually matched to each case based on the center, patient age, and year of the transplant. We identified 185 cases of probable and proven IA and 651 control subjects. The median date of IA after the transplant was 133 days, with 35 cases (19%) of early IA (before day 40), 33 cases (18%) of late IA (days 40 to 100), and 117 cases (63%) cases of very late IA (after day 100). In the multivariate analysis early IA was significantly associated with a lack of engraftment, whereas late and very late IA were significantly associated with more than grade II acute graft-versus-host disease (GVHD); very late IA was also significantly associated with relapse and secondary neutropenia. Two-thirds of IA cases occurred more than 100 days after HSCT with different risk factors from those occurring earlier. Prophylactic strategies should consider the specific risk factors for late and very late IA, especially GVHD, relapse after transplant, and secondary neutropenia.