OBJECTIVES: Leuprolide is one of the most common LH-RH agonists used in advanced prostate cancer. An economic study was conducted to assess which of the existing leuprolide formulations are more cost-effective for the management of prostate cancer in Belgium. METHODS: Major database searches identified clinical trials of leuprolide 1- (1M), 3- (3M) and 6-monthly (6M); no differences in efficacy and safety were found. We conducted cost-minimisation analysis using an Excel model. Adherence and safety were not significantly different; costs of leuprolide, specialist consultations and diagnostics were considered during up to 12 months follow-up. Costs were available for 2009, not discounted due to short time horizon. The perspective was that of the public payer: RIZIV/NAMI. RESULTS: 1M was the most expensive treatment at 3,746€. The 3M formulation was 1,739€ less costly and 6M offered cost-savings of 2,126€ compared to 1M and 387€ versus 3M. Cost of leuprolide was also the highest for 1M: 1,628€; 3M cost 1,117€ and 6M 1,097€. Total costs were associated with the frequency of visits for injection and monitoring. 1M required 12 visits, 3M 4.4 visits, and 6M 2.1 visits. 36.7% [95%CI: 34.7-38.5%] additional visits could be funded with the savings resulting from switching eligible patients from 1M and 3M to 6M. Results were stable in one-way sensitivity analyses. In the probabilistic sensitivity analysis the 95% uncertainty intervals for total costs were 3,497-4,019€, 1,802-2,000€ and 1,429-1,519€ for 1M, 3M and 6M, respectively. CONCLUSIONS: The 6-monthly formulation offers the greatest cost-savings in Belgium.