The effects of low persistence on fracture risk have not been fully addressed. The objectives of this study were to describe the persistence and compliance with bisphosphonates and to evaluate the association with fracture risk. The General Practice Research database was used to identify patients >or=18 yr of age prescribed alendronate or risedronate. The follow-up was divided into periods of current and past use. Time-dependent Cox regression was used. The study population included 44,531 patients; 58.3% of the patients continued bisphosphonate treatment for >1 yr and 23.6% for >5 yr. The risk of hip/femur fracture (adjusted relative rate [RR], 0.78; 95% CI, 0.64-0.94) and osteoporotic fracture (RR, 0.85; 95% CI, 0.76-0.94) were lower with current compared with past bisphosphonate use. The largest reduction in hip/femur and osteoporotic fracture risk was observed in patients treated for at least 6 mo and no reduction in those treated for <6 mo. The risks of hip/femur and osteoporotic fractures followed the pattern of nonosteoporotic fractures in the first 6 mo but then started to reduce after 6-12 mo of treatment. Increased risks of osteoporotic and hip/femur fractures were found in patients with low compliance. Use of bisphosphonates was associated with fracture risk reductions after 6-12 mo of treatment, but only 58% of the patients were treated for at least 1 year. Improvement in long-term persistence to bisphosphonate treatment may be important to reduce the impact of osteoporosis-related fractures.