OBJECTIVES:  Results from real-world studies suggest reduced hospital length-of-stay, intravenous (IV) length-of-therapy (LOT), and costs in patients with invasive aspergillosis (IA) treated with voriconazole compared to liposomal amphotericin B (LAMB) or caspofungin therapy. We performed a cost analysis comparing voriconazole, LAMB, and caspofungin as first-line treatment for IA among patients with prolonged neutropenia or undergoing bone marrow or hematopoietic stem-cell transplantation (BMT/HSCT) from a payer perspective in Lebanon. METHODS:  A decision analytic model with a 6-week time horizon was constructed to estimate voriconazole, LAMB, and caspofungin treatment costs (2016 US$) in Lebanon. Each treatment pathway was defined by probabilities of event occurrence and clinical outcome costs derived from published literature or local expert opinion. We assumed patients failing first-line voriconazole were switched-to or added-on caspofungin; patients failing first-line LAMB or caspofungin were switched-to or added-on voriconazole. Base-case evaluation included drug management and additional hospitalization costs due to severe adverse events. Treatment success rates were obtained from pivotal clinical trials (voriconazole, 52.8%; LAMB, 50.0%; caspofungin, 33%). First-line treatment duration was assumed 24 days for voriconazole (14-day 4-6mg/kg/d IV followed by 10-day 200mg/BID oral), IV LAMB (3-5mg/kg/d), and IV caspofungin (50-70mg/d); second-line treatment duration was assumed 15 days regardless of therapy. RESULTS:  Results from our model showed considerably lower total treatment costs for voriconazole (LBP14,144,427/$9,411) than LAMB (LBP32,982,623/$21,945) and caspofungin (LBP26,202,736/$17,434) in Lebanon. Voriconazole cost savings primarily resulted from lower drug costs, higher treatment efficacy, and shorter IV LOT compared to LAMB and caspofungin. First-line voriconazole therapy remained cost saving even when the entire voriconazole treatment course was administered intravenously. Cost drivers included treatment efficacy and i.v. drug per-day costs (voriconazole LBP462,914/$308; LAMB LBP1,130,232/$752; caspofungin LBP766,513/$510). CONCLUSIONS:  Results from this study suggest that voriconazole is cost-saving compared to LAMB and caspofungin in the treatment of IA from payer perspectives in Lebanon.