OBJECTIVES: Published real-world studies suggest voriconazole may provide reduced length-of-stay, intravenous (IV) length-of-therapy (LOT), and costs compared to liposomal amphotericin B (LAMB) and caspofungin in invasive aspergillosis (IA) patients. We performed a cost analysis of voriconazole versus LAMB and caspofungin as first-line antifungal treatment for IA among patients with prolonged neutropenia or undergoing bone marrow or hematopoietic stem-cell transplantation (BMT/HSCT) from payer perspective in Kingdom of Saudi Arabia (KSA). METHODS: A decision analytic model with a 6-week time horizon was constructed to estimate potential treatment cost of alternative interventions voriconazole, LAMB, and caspofungin. Each treatment pathway was defined by probabilities of an event occurrence and costs (in US$) of clinical outcomes derived from published literature, clinical trials, and local expert opinions. Patients who failed first-line voriconazole were assumed to have a switch-to or add-on of caspofungin; patients who failed LAMB or caspofungin were assumed to have a switch-to or add-on of voriconazole. Base-case evaluation included drug management costs and additional hospitalization costs due to severe adverse events. RESULTS: Based on the clinical trial treatment success rates of 52.8% for voriconazole, 50.0% for LAMB, and 33% for caspofungin, as well as assuming first-line 14-day IV treatment and 10-day oral treatment for voriconazole, 24-day IV treatment for LAMB, and 24-day IV treatment for caspofungin in KSA, voriconazole had a considerable lower total treatment cost ($7,654) than LAMB ($16,564) and caspofungin ($17,362).  Cost savings were primarily due to the lower drug cost, higher treatment efficacy, and shorter IV length-of-therapy associated with voriconazole. The cost advantage of voriconazole persists through a full-course of the first-line treatment with voriconazole IV (24 days in KSA), even without oral treatment. CONCLUSIONS: This study suggests that voriconazole is cost-saving compared to LAMB and caspofungin in the treatment of IA from payer perspectives in KSA.