The long-term efficacy and safety of implantable atrial defibrillator (IAD) therapy in patients with AF and cardiovascular disease is unclear. The aim of this study was to evaluate the efficacy and safety of IAD therapy in patients with and without coexisting cardiovascular disease. In 115 patients implanted with an IAD, 85 patients had cardiovascular disease: 41 (48%) patients had 1 cardiovascular abnormality, 29 (35%) patients had 2, 13 (15%) patients had 3, and 2 (2%) patients had 4 different cardiovascular abnormalities. The device was programmed into a rhythm monitoring mode for the first 3-month postimplant period. All defibrillation therapy was performed under physician supervision to monitor safety and efficacy. After this initial monitoring period, patients were allowed to activate their device away from the hospital or clinic. A total of 357 spontaneous AF episodes occurred in 83 (72%) patients during observed operation and the mean shock efficacy was 93.5+/-20.3% (lower 95% confidence interval [CI] 89.8%). As of the lastfollow-up, 58 (55%) patients had transition to receive nonphysician observed therapy. Forty-two (72%) patients had experienced 332 episodes of AF for which theyhad received device therapy away from the hospital/clinic (mean shock efficacy 90.5+/-39.7%). The presence of hypertension, valvular heart disease, and ischemic heart disease did not affect the shock efficacy of the IAD during physician observed and nonobserved therapy (P > 0.05). However, the presence of congestive heart failure was associated with a lower clinical efficacy during observed and nonobserved therapy (P < 0.05). Overall, 5,262 shocks have been delivered with the IAD without any episode of proarrhythmia. The observed proarrhythmic risk was 0%, with an estimated maximum proarrhythmic risk of 0.06% per shock (95% upper CI). A stand-alone IAD appears to be safe in the presence of cardiovascular disease. The lower clinical efficacy for AF associated with congestive heart failure might be related to a higher rate of early reinitiation of AF after defibrillation.