Background: Bisphosphonates are the class of medication used most widely to treat osteoporosis. Since an article reported that patients who used zoledronic acid, a bisphosphonate, had a higher proportion of atrial fibrillation (AF) in 2007, the issue of bisphosphonates and AF has become a growing concern. Due to the widespread use of bisphosphonates, it is necessary to explore the relationship between bisphosphonates and AF and other cardiovascular diseases. Objective: We aimed to investigate the risk of AF, stroke, or acute myocardial infarction (AMI) associated with the use of the bisphosphonates alendronate and raloxifene in patients with osteoporosis. We also focused our analysis on the impact of different dosing regimens of alendronate. Methods: The National Health Insurance Research Database was used to conduct an 8-year, population-based, retrospective cohort study. The study population comprised women who first took alendronate or raloxifene between 2002 and 2006 and who had a history of osteoporosis and vertebral or spinal fracture. Follow-up was conducted for every patient until the first diagnosis of AF, stroke, or AMI or until the end of the 1-year follow-up period. The Cox proportional hazards model was used to evaluate the association between the risk of cardiovascular disease and the prescription of alendronate or raloxifene. Results: We identified 9609 women who had been prescribed either alendronate (n = 6949) or raloxifene (n = 2660). The patients treated with alendronate were at a lower risk of AF, stroke, or AMI compared with the raloxifene group (AF: hazard ratio [HR] = 0.60 [95% CI, 0.42-0.85]; stroke: HR = 0.47 [95% CI, 0.39-0.57]; AMI: HR = 0.51 [95% CI, 0.36-0.72]). However, when analyzing the groups by different alendronate dosing regimens, those patients who received alendronate 10 mg had a significantly higher risk of AF and stroke compared with patients who received raloxifene (AF: HR = 1.66 [95% CI, 1.12-2.46]; stroke: HR = 1.56 [95% CI, 1.23-1.98]). The alendronate 70-mg group demonstrated a lower risk of cardiovascular disease, be it AF, stroke, or AMI (AF: HR = 0.28 [95% CI, 0.18-0.43]; stroke: HR = 0.23 [95% CI, 0.18-0.30]; AMI: HR = 0.28 [95% CI, 0.18-0.41]). When we assigned alendronate 10 mg as the reference group, the alendronate 70 mg group had a lower risk of 3 cardiovascular diseases (AF: HR = 0.17 [95% CI, 0.10-0.27]; stroke: HR = 0.16 [95% CI, 0.12-0.22]; AMI: HR = 0.21 [95% CI, 0.13-0.35]). Conclusions: Alendronate 10 mg was associated with a higher risk of cardiovascular disease than alendronate 70 mg. Further studies are required to investigate this relationship.