OBJECTIVES: Three formulations of leuprolide, an established LH-RH agonist are used in the management of advanced prostate cancer. In order to inform clinical practice, the economic impact of the different formulations and dosing schedules were evaluated for Austria, Belgium, Czech Republic, Hungary, Italy, Latvia, Netherlands, Poland and Portugal. METHODS: Database searches identified 10 clinical trials of leuprolide 1-monthly (1M), 3-monthly (3M) and 6-monthly (6M) with Atrigel®, requiring 6, 4 and 2 hospital treatment visits respectively. Due to reported comparable efficacy, safety and adherence, cost-minimisation analysis was conducted. Costs of the product, specialist consultations and diagnostics (converted to 2010 euros) were considered during up to 12 months follow-up. The perspective was that of public payers. RESULTS: The review showed that with the use of leuprolide 1M, 3M and 6M the respective percentage of patients achieving testosterone suppression of ≤50ng/dl was 93.3%, 98.3% and 97.3%  (p>0.05). However, 6M was the least cost treatment option, with average total annual costs from 788€ (Poland) to 1839€ (Portugal). The 3M option was 2.5% (Hungary) to 37.6% (Belgium) higher than 6M cost; while 1M formulation had the highest cost: 15.6% and 151.6% more than 6M for those countries, respectively. The 3M option was 11.2% to 45.3% less expensive than 1M. The cost drivers were the frequency of visits for injection and monitoring. The study showed that up to 50% additional visits could be funded with the savings resulting from switching eligible patients from 1M and 3M to 6M. Results were robust in one-way sensitivity analyses, as well as probabilistic sensitivity analysis. CONCLUSIONS: Leuprolide acetate with Atrigel® 1M, 3M and 6M formulations offer comparable efficacy and safety. However, driven by the frequency of visits, the 6-monthly formulation offers the greatest cost-savings for prostate cancer patients in the European countries studied.