(1) Background: Aspergillus spp. is a widely distributed filamentous fungus in the environment due to its high sporulation capacity. Currently, invasive aspergillosis (IA) is the most common invasive fungal infection in patients with hematologic malignancies, with high rates of mortality and morbidity. The multifactorial nature of the disease requires appropriate risk stratification to enable the most appropriate preventive measures to be adapted and implemented according to the characteristics of the patient. In this sense, the present research aims to identify recent risk factors and environmental control measures against invasive aspergillosis to establish preventive actions to reduce the incidence of invasive aspergillosis in hospitals. (2) Methods: We conducted a qualitative systematic review of the scientific literature on environmental risk factors and preventive measures for invasive aspergillosis in patients with hematologic malignancies. The Medline, Cochrane, and Scopus databases were consulted, following the PRISMA and STROBE guidelines. (3) Results: Adequate implementation of environmental control measures is presented as the most efficient intervention in terms of prevention to decrease the incidence of invasive aspergillosis in hospitals. Neutropenia, fungal contamination, insufficient environmental control measures in hospital and home settings, length of hospital stay, and anemia, are identified as independent risk factors. We show that HEPA, LAF, and Plasmair® systems are suitable methods to reduce the concentration of airborne fungal spores. Antifungal prophylaxis did not significantly influence IA reduction in our study. (4) Conclusions: Proper professional training and environmental control measures in hospitals are essential for the prevention of invasive aspergillosis. We should optimize risk stratification for patients with hematologic malignancies. Antifungal prophylaxis should be complementary to environmental control measures and should never be substituted for the latter. Studies should also be undertaken to evaluate the efficiency of environmental control measures against IA at patients' homes.
Keywords: aspergillosis; environmental control; neutropenia; primary prevention; risk factors.