OBJECTIVES: Atypical femoral diaphyseal fracture and long-term alendronate use may be linked. The protective effect and the risk of atypical femoral fracture of alendronate and other anti-osteoporosis drugs in older Taiwanese women were evaluated. METHODS: A population-based retrospective cohort was obtained from the 2000 to 2009 Taiwan National Health Insurance (NHI) data. Subjects hospitalized with vertebral or hip fracture to 2007 were selected using 2000 as a run-in year to identify incident osteoporotic fractures. All patients receiving alendronate, raloxifene, calcitonin salmon, or teriparatide after index fracture diagnosis formed the treated cohort. An untreated cohort was obtained accordingly. Patients were followed until endpoint (hospitalization for hip fracture or atypical femoral diaphyseal fracture) or end of study period. Cox proportional hazards models were used to assess the association between alendronate and other anti-osteoporosis drugs and fracture risks. RESULTS: Among the 11,278 patients (mean age, 77 years), 2,425 (21.5%) received alendronate (mean follow-up, 1228±797 days), 2,694 (23.9%) received other anti-osteoporosis drugs (mean follow-up, 1069±639 days), and 6,159 (54.6%) remained untreated (mean follow-up, 1357±835 days). Head-to-head comparisons revealed alendronate’s superiority (HR 0.77, 95% CI 0.62–0.95) over other anti-osteoporosis drugs in hip fracture prevention.  The risk of subsequent hip fracture was significantly reduced (adjusted HR 0.27, 95% CI 0.15–0.78) in long-term alendronate users.  Risk of atypical femoral fracture was similar for alendronate versus other anti-osteoporosis drugs (adjusted HR 0.49, 95% CI 0.40–1.47). Short- or long-term alendronate use was not associated with higher risk of atypical femoral fractures. CONCLUSIONS: Alendronate poses no greater risk of atypical femoral fracture than other agents, and its benefits in reducing hip fracture risk significantly outweigh this concern.