BACKGROUND AND AIMS: Recurrent aphthous ulcers (RAU) in the oral cavity are painful, causing substantial morbidity in the US and elsewhere in the world. Despite this, there is a lack of population-based studies representative of the US national adult population to describe the epidemiology, and estimate the true disease burden and association with independent risk factors. Although several studies have investigated the role of various factors in RAU etiology, the epidemiology and etiology of RAU remain unclear. This study aims to establish the prevalence and describe the epidemiology of RAU in adults. METHODS: Data from the Third National Health and Nutrition Examination Survey (NHANES III) were analyzed in SUDAAN using multivariable logistic regression, modeling RAU occurrences. RESULTS: Overall, for all Americans regardless of age, prevalence of RAU was 1030 per 100,000 people (95% CI 830-1220). The prevalence of RAU among adults was 850 per 100,000 (95% CI 630-1070). The lower vestibule was the most commonly involved site. Multivariable analyses suggested that adjusted odds of RAU were greatest for those 17-29 years of age (adjusted OR 2.7; 95% CI 1.4-5.5), for men (adjusted OR 1.7; 95% CI 0.9-2.8), and for those with low serum insulin levels (OR 2.0; 95% CI 0.9-4.4). Never smokers had greater risk of RAU (OR 9.2, 95% CI 2.8-30.1) compared with those who smoked more than 10 cigarettes per day. CONCLUSION: This study establishes the prevalence of RAU among adults in the US and demonstrates that whereas cigarette smoking is associated with lesser odds, low insulin levels might be independently associated with greater odds of RAU.