OBJECTIVES: Gaucher disease (GD), a lysosomal storage disorder caused by mutations in the gene encoding the enzyme glucocerebrosidase, requires life-long treatment with enzyme replacement therapy (ERT). Currently available ERTs include imiglucerase, velaglucerase alfa, and taliglucerase alfa. Taliglucerase alfa is the first plant cell-expressed beta-glucocerebrosidase ERT approved for adults with type 1 GD. The purpose of this analysis was to model the potential budget impact of taliglucerase alfa therapy for GD in the USA. METHODS: A hypothetical budget impact model analysis was performed, based on total estimated number of GD patients treated, treatment costs, and estimated treatment distribution of each ERT. Costs in USD ($) per 200-unit vial were based on wholesale acquisition costs on ReadyPrice and Medi-Span databases. Annual costs were calculated using number of vials required. Actual cost savings may vary with factors beyond drug acquisition costs (eg, rebate programs) and may not reflect actual costs paid. RESULTS: The estimated number of GD patients treated with ERT in the USA was 3,000. Drug costs for 200 units of ERT were: taliglucerase alfa–$595, velaglucerase alfa–$675, and imiglucerase–$793. Annual costs/patient were estimated at $328,440, $372,600, and $437,736 for taliglucerase alfa, velaglucerase alfa, and imiglucerase, respectively. Switching 50 patients to taliglucerase alfa, assuming same market share as national average, could save up to $4 million annually. The US healthcare system could save ~$100,000/patient annually if patients were switched to taliglucerase alfa. A 20% increase in the number of patients receiving taliglucerase alfa could translate to an overall savings of ~$46 million annually. CONCLUSIONS: Taliglucerase alfa has the potential to provide a cost-saving alternative to other ERTs. This study was sponsored by Pfizer. Editorial support was provided by Peloton Advantage, LLC with funding from Pfizer.