In the RAte Control versus Electrical cardioversion for persistent atrial fibrillation (RACE) study, 522 patients were randomized to either rate or rhythm control therapy. Lone atrial fibrillation (AF) was present in 89 patients. Demographics, cardiovascular mortality and morbidity, and quality of life were compared between patients with lone AF and those with underlying structural heart disease. Patients with lone AF were significantly younger (65 +/- 10 vs 69 +/- 8 years) and had fewer complaints of fatigue (p = 0.01) and dyspnea (p = 0.005). With lone AF, quality-of-life scores were higher on almost all 8 Medical Outcomes Study Short-Form health survey questionnaire subscales, and comparable to healthy, age- and gender-matched controls. Mean follow-up was 2.3 +/- 0.6 years. Cardiovascular end points occurred in 9 patients with lone AF (10%), consisting of death (all bleedings) 3%, thromboembolic complications in 3%, nonfatal bleeding in 2%, and pacemaker implantation in 2%, but no heart failure and severe adverse effects due to antiarrhythmic drugs occurred. End points occurred in 95 patients (22%) with underlying diseases. Heart failure and severe adverse effects from drugs did not occur in patients with lone AF in this study. Despite the absence of demonstrable cardiovascular and cerebrovascular disease, lone AF is associated with bleeding and thromboembolism.