OBJECTIVES: To analyze the adherence of once-yearly intravenous zolendronic acid for osteoporosis. MATERIALS AND METHODS: The subjects were 322 osteoporotic patients who received more than single infusion of zolendronic acid. On clinical assessment, we assessed adherence. The changes of bone mineral density (BMD) and bone turnover marker were measured before and after infusion. RESULTS: Reinfusion rate was 48.4% (109/225) at second infusion, and 51.3% (41/80) at third infusion. Adverse event at each time was 161 (42.1%) cases, 30 (27.5%) cases, and 8 (19.5%) cases, respectively. The measured mean BMD change was significantly increased (P-value<0.001). CONCLUSIONS: In this study, once-yearly intravenous zolendronic acid for 2 years was safe and efficacious in terms of BMD and bone turnover marker. The adherence was higher than most published studies of adherence to oral bisphosphonates, but lower than optimal. Physicians should fully explain to patients about medications and educate to improve their adherence.