Cardiac resynchronization therapy (CRT) may diminish atrial fibrillation (AF) burden in patients with chronic heart failure (HF). Each of 27 patients without permanent AF in whom CRT implantation was unsuccessful was paired with 2 active CRT patients-1 responder and 1 nonresponder-based on age, gender, cause of HF, and history of paroxysmal AF. Device-documented high atrial rates and mode-switching episodes were tabulated during a median follow-up of 386 days. CRT responders had significantly improved left ventricular (LV) ejection fraction and New York Heart Association functional class compared with nonresponders and controls. Left atrial dimension change was similar among the groups (+0.03 +/- 0.92 cm controls; -0.18 +/- 0.80 cm responders; -0.11 +/- 1.01 cm nonresponders) despite a significant reduction in mitral regurgitation in responders compared with nonresponders. There was no significant difference in AF burden between controls and patients who underewent CRT when indexed over time. Median AF-free follow-up was significantly longer in patients who underwent CRT without a history of AF (log-rank p = 0.04), but no differences were seen in the overall cohorts. In conclusion, despite inducing LV reverse remodeling and clinical improvement, CRT does not appear to decrease AF burden in responders compared with nonresponders or matched controls in whom CRT implantation failed. CRT may, however, delay onset of new AF.