We sought to establish the safety and feasibility of a clinical pathway for the outpatient initiation of antiarrhythmic medications (AAMs) for the maintenance of sinus rhythm in patients with atrial fibrillation (AF) or atrial flutter (AFl). AAMs are frequently utilized to maintain sinus rhythm in patients with AF or AFl. Although they are often initiated in an outpatient setting, there is little prospective evidence for the safety of this approach. Patients with a history of AF or AFl were prospectively monitored with an event recorder during 409 AAM initiation trials. All AAMs were initiated in sinus rhythm. Patients transmitted a recording (30 seconds) once daily for 10 consecutive days. Amiodarone was used for 212 patients (51.8%), 127 (31.1%) received a type 1C AAM, 37 (9.0%) received sotalol, and 33 (8.1%) received a type 1A AAM. Adverse events occurred in 17 patients (3 died, 3 had bradycardia that required permanent pacemaker implantation, and 11 had bradycardia requiring a decrease in the dose of antiarrhythmic or rate-controlling medication). Most events were due to bradycardia in patients who received amiodarone. There was a significant association between amiodarone-associated bradycardia and women. The only event that occurred during the first 48 hours was an episode of bradycardia in a patient who received amiodarone and was managed as an outpatient. The outpatient initiation of AAMs for patients with a history of AF or AFl while in sinus rhythm is associated with significant risk. Most adverse events occurred beyond the usual time period for in-hospital monitoring of the initiation of AAMs.