OBJECTIVES To assess the impact of genotyping acute myeloid leukemia (AML) patients for CYP2C19*17 gene variant status prior to induction-consolidation therapy from the perspective of a United States (U.S.) payer. METHODS Developed to aid U.S. payers regarding the budgetary impact of DNA genotyping, this model examines the predicted economic outcomes of a hypothetical cohort of 100 neutropenic AML patients under two alternatives:  (1) standard voriconazole prophylaxis and (2) genotyping patients for targeted prophylaxis. Published allelic frequencies estimate 27% of the general population may have at least one *17 allele. The presence of the CYP2C19*17 allele results in more rapid metabolism and clearance of voriconazole, which can lead to underdosing and ineffective prophylaxis on the standard regimen. The incidence of invasive fungal infection is 15% without effective prophylaxis and is reduced to 6.6% upon adequate prophylaxis. Targeted prophylaxis based on genotyping prescribes an alternative drug or higher voriconazole dose in patients with the *17 allele. Further model parameters were taken from published literature and 2014 CMS Laboratory Fee Schedule.  RESULTS The average total cost of care for AML patients receiving standard versus targeted voriconazole prophylaxis was $46,795 and $46,385 per patient, respectively. In addition to the $410 saved per patient, the number of invasive fungal infections was reduced from 6.6 to 4.3 by targeting prophylaxis based on patient genotype. The deterministic sensitivity analysis showed that the savings is most dependent on the incidence of invasive fungal infection, cost of treating an invasive fungal infection, and frequency of *17 in the population. CONCLUSIONS Genotyping AML patients for CYP2C19*17 prior to induction-consolidation is expected to be cost-neutral or potentially cost-saving by reducing the incidence of invasive fungal infections compared to standard prophylaxis. These results may mitigate potential budgetary concerns, thereby reducing barriers to a test that can be clinically beneficial to AML patients.