Background-There are a paucity of data about the long-term natural history of adult Wolff-Parkinson-White syndrome (WPW) patients in regard to risk of mortality and atrial fibrillation. We sought to describe the long-term outcomes of WPW patients and ascertain the impact of ablation on the natural history. Methods and Results-Three groups of patients were studied: 2 WPW populations (ablation: 872, no ablation: 1461) and a 1:5 control population (n=11 175). Long-term mortality and atrial fibrillation rates were determined. The average followup for the WPW group was 7.9±5.9 (median: 6.9) years and was similar between the ablation and nonablation groups. Death rates were similar between the WPW group versus the control group (hazard ratio, 0.96; 95% confidence interval, 0.83-1.11; P=0.56). Nonablated WPW patients had a higher long-term death risk compared with ablated WPW patients (hazard ratio, 2.10; 95% confidence interval: 1.50-20.93; P<0.0001). Incident atrial fibrillation risk was higher in the WPW group compared with the control population (hazard ratio, 1.55; 95% confidence interval, 1.29-1.87; P<0.0001). Nonablated WPW patients had lower risk than ablated patients (hazard ratio, 0.39; 95% confidence interval, 0.28-0.53; P<0.0001). Conclusions-Long-term mortality rates in WPW patients are low and similar to an age-matched and gender-matched control population. WPW patients that underwent the multifactorial process of ablation had a lower mortality compared to nonablated WPW patients. Atrial fibrillation rates are high long-term, and ablation does not reduce this risk.