OBJECTIVES: To determine if patients receiving oral bisphosphonates are at excess risk of atrial fibrillation (AF), stroke and myocardial infarction. DESIGN: Register-based restricted cohort study. SETTING: National Hospital Discharge Register and National Prescriptions Database (1995-2005). SUBJECTS: Fracture patients beginning bisphosphonates (n = 15 795) were matched with unexposed fracture patients of the same age, sex and fracture type (n = 31 590). RESULTS: Incidence rates of AF were 16.5/1000 person years in untreated fracture patients and 20.6/1000 person years in bisphosphonate users. An age- and sex-adjusted hazard ratio (HR) of 1.29 (1.17-1.41) was found for probable AF by Cox proportional hazards analysis. The effect size was reduced to HR of 1.18 (1.08-1.29) by adjustment for co-medications and comorbidity. Selective prescribing was suggested by the observation that (i) risks were increased even in patients who stopped therapy after the first packet and (ii) risks were not increased by high adherence. Bisphosphonate-exposed patients were at increased risk of hospital-treated AF [adjusted HR: 1.13 (1.01-1.26)], but the risk amongst bisphosphonate users was inversely proportional to adherence. There was no increased risk of ischaemic stroke and an increased risk of myocardial infarction was not significant after adjustment for comorbidity. CONCLUSIONS: The increased occurrence of AF in fracture patients who are users of oral bisphosphonates should be attributed to targeting of bisphosphonates to patients who are already at increased risk of cardiovascular events.