Objective: Ulipristal acetate has been found to be non-inferior to other pre-operative treatments of uterine fibroids, particularly leuprolide. The objective of this study was to assess the pharmacoeconomic profile of ulipristal acetate compared to leuprolide for the pre-operative treatment of moderate to severe uterine fibroids in women of reproductive age in The Netherlands. The analysis was performed and applied within the framework of the ulipristal acetate submission for reimbursement in 2012. Methods: A decision model was developed to compare the total costs of ulipristal acetate compared to leuprolide, the standard care in The Netherlands. The target population of this study corresponded to the type of patients included in the PEARL II clinical trial; i.e. women of reproductive age requiring pre-operative treatment for uterine fibroids. Sensitivity analysis was implemented, to assess uncertainties. Data regarding costs, effects, and other input parameters were obtained from relevant published literatures, the Dutch Healthcare Insurance Board and expert opinion obtained by means of a panel of experts from several medical centres in The Netherlands. Results: In The Netherlands, the total costs of ulipristal acetate and leuprolide were estimated at €4,216,027 and €4,218,095, respectively. The annual savings of ulipristal acetate were therefore estimated at €2,068. The major driver of this cost difference was the cost of administration for leuprolide. Sensitivity analyses showed that ulipristal acetate mostly remained cost-saving over a range of assumptions. The budget impact analysis indicated that the introduction of ulipristal acetate was estimated to result in cost savings in the first three years following the introduction. The results of this study were used in the decision on reimbursement of ulipristal acetate according to the Dutch Reference Pricing system in 2012. Conclusion: Ulipristal acetate was cost saving compared to leuprolide and has the potential to provide substantial savings on the healthcare budget in The Netherlands.