Bradyarrhythmia requiring permanent pacemaker insertion has been associated with amiodarone use but the effect of amiodarone dose has not been investigated. In order to determine the effect of amiodarone dose on the risk of requiring permanent pacemaker insertion, a cohort of 15,824 subjects with atrial fibrillation (AF) and prior myocardial infarction was established. This study included 1,340 subjects who received a first prescription of amiodarone at > 65 years of age. Cox regression with daily dose and cumulative dose (weighted for recency of exposure) represented by time dependent covariates was performed, adjusting for baseline risk factors and time dependent exposure to other cardiac medications. The incidence of pacemaker insertion was 2.2% per person-year during a mean of 1.8 +/- 1.5 years of follow-up, and 5.2% per person-year during the first 90 days of amiodarone exposure. Amiodarone daily doses > 200 mg were associated with an increased risk during the entire follow-up HR 2.0; 95% CI 1.0 to 4.1) as well as during the first 90 days (HR 3.1; 95% CI 1.1 to 9.0). Cumulative doses greater than the equivalent of continuous therapy with 200 mg per day were also associated with an increased risk (HR 2.8; 95% CI 1.4 to 5.5). Baseline conduction disorder or sinus node dysfunction was the only other significant predictor of pacemaker insertion. This study suggests that there is a dose dependent increased risk of permanent pacemaker insertion associated with amiodarone use that appears to be greatest during the initial months of treatment.