Background: Atrial fibrillation/atrial flutter (AF/AFL) burden increases with increasing duration of AF/AFL history. Hypothesis: Outcomes with dronedarone may also be impacted by duration of AF/AFL history. Methods: In this post hoc analysis of ATHENA, efficacy and safety of dronedarone vs placebo were assessed in groups categorized by time from first known AF/AFL episode to randomization (ie, duration of AF/AFL history): <3 months (short), 3 to <24 months (intermediate), and ≥ 24 months (long). Results: Of 2859 patients with data on duration of AF/AFL history, 45.3%, 29.6%, and 25.1% had short, intermediate, and long histories, respectively. Patients in the long history group had the highest prevalence of structural heart disease and were more likely to be in AF/AFL at baseline. Placebo-treated patients in the long history group also had the highest incidence of AF/AFL recurrence and cardiovascular (CV) hospitalization during the study. The risk of first CV hospitalization/death from any cause was lower with dronedarone vs placebo in patients with short (hazard ratio, 0.79 [95% confidence interval: 0.65-0.96]) and intermediate (0.72 [0.56-0.92]) histories; a trend favoring dronedarone was also observed in patients with long history (0.84 [0.66-1.07]). A similar pattern was observed for first AF/AFL recurrence. No new drug-related safety issues were identified. Conclusions: Patients with long AF/AFL history had the highest burden of AF/AFL at baseline and during the study. Dronedarone significantly improved efficacy vs placebo in patients with short and intermediate AF/AFL histories. While exploratory, these results support the potential value in initiating rhythm control treatment early in patients with AF/AFL.