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Background and Aim: Oral bisphosphonates have been shown to reduce the risk of fractures in patients with osteoporosis. It can be assumed that the clinical effectiveness of oral bisphosphonates depends on persistence with therapy. Methods: The infl uence of persistence with and adherence to oral bisphosphonates on fracture risk in a real-life setting was investigated. Data from 4451 patients with a defi ned index prescription of bisphosphonates were included. Fracture rates within 180, 360, and 720 days after index prescription were compared between persistent and non-persistent patients. In an extended Cox regression model applying multiple event analysis, the infl uence of adherence was analyzed. Persistence was defi ned as the duration of continuous therapy; adherence was measured in terms of the medication possession ratio (MPR). Results: In patients with a fracture before index prescription, fracture rates were reduced by 29% (p = 0.025) comparing persistent and non-persistent patients within 180 days after the index prescription and by 45% (p Ͻ 0.001) within 360 days. The extended Cox regression model showed that good adherence (MPR Ն 0.8) reduced fracture risk by about 39% (HR 0.61, 95% CI 0.47-0.78; p Ͻ 0.01). Conclusions:In patients with osteoporosis-related fractures, good persistence and adherence to oral bisphosphonates reduced fracture risk signifi cantly.