Background An understanding of the risk factors for atrial fibrillation (AF) progression and the associated impacts on clinical prognosis are important for the future management of this common arrhythmia. We aimed to investigate the rate of progression from paroxysmal (PAF) to more sustained subtypes of AF (SAF), the associated risk factors for this progression, and its impact on adverse clinical outcomes. Methods and Results Using data from the Chinese trial Fibrillation Registry study, we included 8290 PAF patients. Half of them underwent initial AF ablation at enrollment. The main outcomes were ischemic stroke/systemic embolism (IS/SE), cardiovascular hospitalization, cardiovascular death, and all-cause mortality. The median follow-up duration was 1091 (704, 1634) days, and progression from PAF to SAF occurred in 881 (22.5%) nonablated patients, while 130 (3.0%) ablated patients had AF recurrence and developed SAF. The incidence rate of AF progression for the cohort was 3.87 (95% confidence interval [CI] = 3.64-4.12) per 100 patient-years, being higher in nonablated compared to ablated patients. Older age, longer AF history, heart failure, hypertension, coronary artery disease, respiratory diseases, and larger atrial diameter were associated with a higher incidence of AF progression, while antiarrhythmic drug use and AF ablation were inversely related to it. For nonablated patients, AF progression was independently associated with an increased risk of IS/SE (hazard ratio [HR] = 1.52, 95% CI = 1.15-2.01) and cardiovascular hospitalizations (HR = 1.40, 95% CI = 1.23-1.58). Conclusion AF progression was common in its natural course. It was related to comorbidities and whether rhythm control strategies were used, and was associated with an increased risk of IS/SE and cardiovascular hospitalization.