Mould infections in hematopoietic stem cell transplant (HSCT) recipients have become a significant cause of mortality. This study analyzed data from 5589 HSCT recipients at the Fred Hutchinson Cancer Research Center (FHCRC) from 1985 to 1999. Invasive aspergillosis (IA) incidence increased after 1992, with non-fumigatus Aspergillus, Fusarium, and Zygomycetes infections rising in the late 1990s, especially in patients with multiple transplants. Scedosporium infections were common in neutropenic patients, while Zygomycetes infections occurred later, often in the context of graft-versus-host disease (GVHD). The 1-year survival rate for all mould infections was approximately 20%. The study highlights the increasing importance of amphotericin B-resistant organisms and the varying risks and outcomes of infections with different filamentous fungi. The incidence of IA increased among both allograft and autograft recipients, with a notable rise in autologous recipients in 1998. IA was most commonly caused by A. fumigatus, but non-fumigatus Aspergillus species became more prevalent after 1995. Non-Aspergillus moulds, including Fusarium, Zygomycetes, and Scedosporium, also increased in frequency, with Fusarium and Zygomycetes infections more common in patients with multiple transplants. Scedosporium infections were more likely to disseminate, while Zygomycetes infections were more frequently isolated to the sinuses. Risk factors for IA included age >40 years, non-chronic myelogenous leukemia (CML-CP) or hematologic malignancy in first remission, and HLA-mismatched or unrelated donor transplants. Zygomycetes infections were more common in the first 30 days after transplantation, while Fusarium infections were more frequent later. The 1-year survival rate was poor for all mould infections, with Scedosporium infections having the worst prognosis. The study emphasizes the need for improved prevention and treatment strategies for mould infections, particularly for amphotericin B-resistant organisms. New antifungal agents and better diagnostic strategies are needed to address the increasing prevalence and severity of these infections in HSCT recipients.Mould infections in hematopoietic stem cell transplant (HSCT) recipients have become a significant cause of mortality. This study analyzed data from 5589 HSCT recipients at the Fred Hutchinson Cancer Research Center (FHCRC) from 1985 to 1999. Invasive aspergillosis (IA) incidence increased after 1992, with non-fumigatus Aspergillus, Fusarium, and Zygomycetes infections rising in the late 1990s, especially in patients with multiple transplants. Scedosporium infections were common in neutropenic patients, while Zygomycetes infections occurred later, often in the context of graft-versus-host disease (GVHD). The 1-year survival rate for all mould infections was approximately 20%. The study highlights the increasing importance of amphotericin B-resistant organisms and the varying risks and outcomes of infections with different filamentous fungi. The incidence of IA increased among both allograft and autograft recipients, with a notable rise in autologous recipients in 1998. IA was most commonly caused by A. fumigatus, but non-fumigatus Aspergillus species became more prevalent after 1995. Non-Aspergillus moulds, including Fusarium, Zygomycetes, and Scedosporium, also increased in frequency, with Fusarium and Zygomycetes infections more common in patients with multiple transplants. Scedosporium infections were more likely to disseminate, while Zygomycetes infections were more frequently isolated to the sinuses. Risk factors for IA included age >40 years, non-chronic myelogenous leukemia (CML-CP) or hematologic malignancy in first remission, and HLA-mismatched or unrelated donor transplants. Zygomycetes infections were more common in the first 30 days after transplantation, while Fusarium infections were more frequent later. The 1-year survival rate was poor for all mould infections, with Scedosporium infections having the worst prognosis. The study emphasizes the need for improved prevention and treatment strategies for mould infections, particularly for amphotericin B-resistant organisms. New antifungal agents and better diagnostic strategies are needed to address the increasing prevalence and severity of these infections in HSCT recipients.