OBJECTIVES: Poor compliance with oral bisphosphonates leads to increased risk of vertebral and hip fractures in post-menopausal osteoporotic patients. Annual dose of Zoledronic acid significantly decreased risk of fractures as compared to placebo. The objective of this study was to evaluate a long-term cost-utility of the two strategies. METHODS: Markov model was constructed and first-order microsimulation was run in order to compare long term health-economic impact of treatments with Zoledronic acid and oral bisphosphonates in Czech patients. Rather than clinical efficacy, the model considered real-life effectiveness of both treatments associated with medication compliance. RESULTS: Compared to oral bisphosphonates the treatment with Zoledronic acid showed systematically improved effectiveness expressed as QALY gained throughout the life expectancy.  The incremental cost-effectiveness of the Zoledronic acid is for 50 years of age below €25,708 per QALY gained and decreases sharply for patients above 65 years, resulting in distinctly improved incremental cost-effectiveness ratio below €6442 per QALY gained. CONCLUSIONS: From the age 65 on, patients should be preferentially treated with Zoledronic acid rather than oral bisphosphonates.