OBJECTIVES: To estimate the budget impact of changing the market shares of liposomal amphotericin B (L-AmB) and amphotericin B lipid complex (ABLC) for the treatment of invasive fungal infections (IFIs) in a US hospital. METHODS: An Excel-based budget impact model was developed to estimate the costs associated with using L-AmB and ABLC for treating adult patients with Aspergillus, Candida and Cryptococcus spp. infections who are refractory to or intolerant of conventional amphotericin B. The model was built from a hospital perspective, and included drug acquisition costs and costs for treating drug-related adverse events (AEs) within a hospital stay. The treatment duration of L-AmB and ABLC and rates of AEs for these two treatments were mainly obtained from a retrospective study of these two drugs in the target population using Cerner’s Health Facts data. Treatment costs of AEs were obtained from publicly available sources. The budget impact (2011USD) was evaluated by changing the market share of L-AmB and ABLC from 50/50% to 80/20%. One-way sensitivity analyses were conducted by varying drug cost, treatment duration, and rates and costs of AEs. RESULTS: The per-patient costs associated with L-AmB and ABLC during one hospital stay were $14,563 and $16,748, respectively. Cost of AEs attributed to 68.7% of the costs for L-AmB and 85.4% for ABLC. In a hypothetical hospital with 100 annual admissions of patients using one of these two drugs for fungal infections, changing the market shares from 50/50% for L-AmB and ABLC, respectively, to 80/20% yielded a cost saving of $65,561. Sensitivity analyses indicated that the results were robust to changes in input parameter values. CONCLUSIONS: This study suggests that hospitals can realize cost savings by substituting ABLC with L-AmB in the treatment of invasive fungal infections. The cost savings are driven by the lower rates of AEs associated with L-AmB compared to ABLC.