OBJECTIVES: Several studies have demonstrated that compliant and long-term use of bisphosphonates is necessary to realize full benefits of treatment. In particular, a progressive relation between compliance (medication possession ratio above 80%) and fracture risk reduction has been found (Siris, Mayo Clin Proc 2006;81:1013-22 and Penning, Osteoporos Int 2008;19:511-17). Taking into account patient compliance, we compared the effectiveness and costs of zoledronic acid (ZOL) versus weekly alendronate & risedronate and monthly ibandronate therapies over 3 years in the prevention of postmenopausal osteoporotic fractures from the NHS perspective of Turkey, using Number Needed to Treat (NNT) approach. METHODS: NNT values (1 / (placebo fracture risk – treatment fracture risk) for vertebral (VF), non-vertebral (NVF) and hip fractures (HF) were derived as a function of fracture risks and compliance rates associated with each therapy. Both drug costs and efficacies were adjusted to compliance rates. Relative risks and placebo incidences of each fracture type were obtained from the clinical trials, meta-analyses from NICE reviews, and costs were gathered from local price database. Annual compliance rates were taken from the literature (Willemijn, Cur Med Res Opin 2008;24:3217-22). RESULTS: Compared to each oral bisphosphonate (OB), ZOL generated the lowest clinical NNTs for all fracture sites. Under conservative compliant patient rate of 50% for weekly and 75% for monthly OBs, cost of treatment to prevent one fracture in 3 years was €30,625 (VF) and €160,400 (HF) for ZOL; €76,800 (VF) and €272,900 (HF) for branded alendronate; €75,825€ (VF) and €269,325€ (HF) for generic alendronate; €170,250 (VF) and €783,400 (HF) for risedronate; and €65,725 (VF) for ibandronate. Sensitivity analyses were performed. CONCLUSIONS: In the Turkish setting, compared to all OBs once-yearly administered ZOL was dominantly the most cost-effective treatment regardless of fracture type upto a level of 90% compliance with oral therapies.