Background: The current healthcare climate demands pharmacoeconomic evaluations for different treatment strategies incorporating drug acquisition costs, costs incurred for hospitalisation, drug administration and preparation, diagnostic and laboratory testing and drug-related adverse events (AEs). Here we evaluate the pharmacoeconomics of voriconazole versus liposomal amphotericin B as first-line therapies for invasive aspergillosis (IA) in patients with haematological malignancy and prolonged neutropenia or who were undergoing haematopoietic stem-cell transplantation in Germany or Spain. Methods: A decision analytic model based on a decision tree was constructed to estimate the potential treatment costs of voriconazole versus liposomal amphotericin B. Each model pathway was defined by the probability of an event occurring and the costs of clinical outcomes. Outcome probabilities and cost inputs were derived from the published literature, clinical trials, expert panels and local database costs. In the base case, patients who failed to respond to first-line therapy were assumed to experience a single switch between comparator drugs or the other drug was added as second-line treatment. Base-case evaluation included only drug-management costs and additional hospitalisation costs due to severe AEs associated with first-and second-line therapies. Sensitivity analyses were conducted to assess the robustness of the results. Cost estimates were inflated to 2011 euros ((sic)). Results: Based on clinical trial success rates of 52.8% (voriconazole) and 50.0% (liposomal amphotericin B), voriconazole had lower total treatment costs compared with liposomal amphotericin B in both Germany ((sic)12,256 versus (sic)18,133; length of therapy [LOT] = 10-day intravenous [IV] + 5-day oral voriconazole and 15-day IV liposomal amphotericin B) and Spain ((sic)8,032 versus (sic)10,516; LOT = 7-day IV + 8-day oral voriconazole and 15-day IV liposomal amphotericin B). Assuming the same efficacy (50.0%) in first-line therapy, voriconazole maintained a lower total treatment cost compared with liposomal amphotericin B. Cost savings were primarily due to the lower drug acquisition costs and shorter IV LOT associated with voriconazole. Sensitivity analyses showed that the results were sensitive to drug price, particularly the cost of liposomal amphotericin B. Conclusions: Voriconazole is likely to be cost-saving compared with liposomal amphotericin B when used as a first-line treatment for IA in Germany and Spain.