Whereas smoking is a major risk factor for periodontal disease, the role of smokeless tobacco is unclear. The purpose of this US population-based study of 12,932 adults participating in the Third National Health and Nutrition Examination Survey was to evaluate the association between smokeless tobacco use and severe active periodontal disease. Univariable and multivariable logistic regression modeling quantified the associations between tobacco use and severe active periodontal disease. All adults and never-smokers who currently used smokeless tobacco were twice as likely to have severe active periodontal disease at any site [respective odds ratios (OR(Adj)) and 95% confidence intervals: OR(Adj) = 2.1; 1.2-3.7 and OR(Adj) = 2.1; 1.0-4.4] or restricted to any interproximal site [respective OR(Adj) = 2.1; 1.0-4.2 and OR(Adj) = 2.3; 0.9-6.3], simultaneously adjusted for smoking, age, race, gender, diabetes, and having a dental visit in the past year. These results indicate that smokeless tobacco may also be an important risk factor for severe active periodontal disease.