OBJECTIVE To explore the efficacy and safety of intravenous itraconazole for patients undergoing intensive chemotherapy or hematopoietic stem cell transplantation in different strategies. METHODS Based on multicenter, observational data, the efficacies of antifungal therapy for patients with persistent fever and suspected IFD in different strategies were calculated retrospectively, and the factors associated with the response of antifungal therapy were explored by logistic analysis. RESULTS In accordance with the latest published diagnostic criteria and treatment consensus in China, there were 2 patients who were diagnosed as proven IFD ultimately, 20 probable IFD, 19 possible IFD and 133 undefined IFD, respectively. Accordingly, the response rates in targeted therapy for proven/probable IFD patients, diagnostic-driven therapy for possible and undefined IFD patients with clinical or microbiological evidence of IFD, and empirical therapy for undefined patients without any evidence of IFD were 50.0%, 57.4% and 13.5%, respectively (P<0.01). And the multivariable analysis indicated that the presence of radiological or microbiological evidence of IFD before or after the initiation of antifungal therapy was markedly associated with the response to antifungal therapy (P<0.01). The incidence of itraconazole related adverse effect was only 2.9%. CONCLUSIONS Itraconazole injection was an effective and safe agent in targeted and diagnostic- driven antifungal therapy for immunocompromised or neutropenic febrile patients with hematological malignancies.