OBJECTIVES: In clinical trials zoledronic acid has shown higher efficacy in HCM treatment than pamidronate, currently the drug most widely used. This study evaluated both treatment options from an economic perspective. METHODS: The main outcome measures were incremental cost-efficacy ratios of zoledronic acid 4 mg vs. pamidronate 90 mg perfusions. From the hospital perspective, data on direct, short-term variable resources consumed during drug administration were collected from seven Spanish hospitals using a structured questionnaire. Efficacy data (rate and duration of complete response) were extracted from controlled clinical trials. RESULTS: In total the participating hospitals treated 271 patients/year (93% in outpatient infusion sites). Apart from a price difference of €65.97, differences in resource consumption were related to perfusion times and subsequent demand on personnel, and certain supplies. Time taken for perfusion preparation through to its finalization was considerably longer with pamidronate: for every patient treated with pamidronate on average 3.5 could be treated with zoledronic acid. Under normal clinical practice (permanent patient vigilance and infusion times according to labeling instructions), zoledronic acid required 105 minutes less nursing time, valued at €26.25. Given that also fewer supplies were used (costing €7.29), the total cost difference reduced to an additional €32.43 with zoledronic acid. According to the clinical trials, 18.7 percentage points more patients had a complete response with zoledronic acid than with pamidronate, and average duration of complete response per treatment administered was 4.1 days longer. Thus incremental costs amounted to €173.68 per additional complete response and €7.82 per additional day of complete response. These results are dependent on clinical practice, particularly regarding the savings in personnel costs, and could be higher or lower in circumstances that are different to the most frequent scenario considered here. CONCLUSION: Compared to pamidronate, zoledronic acid considerably shortens treatment time and has an acceptable incremental cost-efficacy ratio.