OBJECTIVES: Published real-world studies suggested voriconazole (Vfend) may provide reduced length-of-stay, intravenous (IV) length-of-therapy (LOT), and costs compared liposomal amphotericin B (LAMB, Ambisome) in invasive aspergillosis (IA) patients. We performed a cost analysis of voriconazole versus LAMB as first-line antifungal treatment for IA among patients with prolonged neutropenia or undergoing bone marrow or hematopoietic stem-cell transplantation (BMT/HSCT) from Brazil public and private payer perspective.   METHODS: A decision analytic model with a 30-day time horizon was constructed to estimate the potential treatment costs of alternative interventions voriconazole versus LAMB. Each pathway in the model was defined by probabilities of an event occurrence and costs of clinical outcomes. Outcome probabilities and cost inputs (in 2014 Brazil Real/R$) were derived from published literature, clinical trials, and recommendations from expert panels. In the base case, patients who failed first-line therapy were assumed to either experience a single switch to or add on with caspofungin as second-line treatment options. Base-case evaluation included drug management costs and additional costs due to severe adverse events. RESULTS: Based on clinical trial treatment success rates of 52.8% (voriconazole) and 50.0% (LAMB), and LOT of 7-day IV + 8-day oral for voriconazole and 15-day IV for LAMB, voriconazole had a considerable lower total treatment cost than LAMB (R$25,060 vs R$100,141 in public sector; R$37,263 vs R$118,503 in private sector).  Cost savings were primarily due to the lower drug cost, higher treatment efficacy, and shorter IV LOT associated with voriconazole. Drug prices and LOT were the main cost drivers. The cost advantage of voriconazole persists through 15 days of IV in the first-line treatment, even without oral treatment. CONCLUSIONS: This study suggests that voriconazole is cost-saving compared to LAMB in the treatment of invasive aspergillosis from both public and private payer perspective in Brazil.