BACKGROUND: Invasive aspergillosis (IA) is a life-threatening infection in immunocompromised patients. In this study, we compared the efficacy of voriconazole containing regimen vs non-voriconazole containing regimen in patients with IA. METHODS: In this retrospective study, we reviewed the medical records of all immunocompromised cancer patients diagnosed with proven or probable IA between February 2012 and March 2018. This trial included 26 patients from the American University of Beirut, Lebanon, 20 patients from Hospital das Clinicas da Faculdade de Medicina, Universidade de São Paulo, Brazil, and 10 patients from St. Luke's International Hospital Tokyo, Japan. RESULTS: A total of 56 patients were analyzed. They were divided into 2 groups voriconazole containing regimen and non-voriconazole containing regimen (90% Amphotericin B based regimen) . Both groups had similar characteristic, age, gender, and immunocompromised status. The majority of patients had underlying leukemia 53%, lymphoma 18%, myeloma 15% and solid tumor 13%. Antifungal primary therapy with voriconazole-containing regimen was associated with better response to treatment (P = 0.003). Survival analysis showed that primary therapy with a voriconazole containing regimen was significantly associated with improved survival (p =0.006). By multivariate logistic regression analysis, mechanical ventilation was predictor of worse outcome (poor response to therapy and increased mortality at 6 weeks), whereas primary treatment with voriconazole containing regimen was associated with improved outcome (OR=0.14; 95% CI 0.03-0.64, P=0.01). CONCLUSIONS: Based on international experience in immunocompromised cancer patients with IA, primary therapy with voriconazole-containing regimen is associated with improved response and survival compared with non-voriconazole amphotericin B based regimen.