Obesity is an important public health problem in the United States. Because of its potential effects on gastric leptin homeostasis, Helicobacter pylori may play a role in regulating body weight. The authors' aim in this study was to examine the association between H. pylori colonization and overweight status. Nonpregnant participants in the Third National Health and Nutrition Examination Survey (1988-1994) aged > or = 20 years who had had H. pylori testing performed and body mass index (weight (kg)/height (m2)) measured were studied. Overweight was defined as a body mass index greater than or equal to 25. On the basis of serologic results, the participants were categorized into three H. pylori status groups: H. pylori-positive and cytotoxin-associated gene A (cagA)-positive (H. pylori+ cagA+), H. pylori-positive and cagA-negative (H. pylori+ cagA-), and H. pylori-negative (H. pylori-). Of the 7,003 subjects with complete body mass index and H. pylori data, 2,634 (weighted percentage, 22.9%) were H. pylori+ cagA+, 1,385 (15.1%) were H. pylori+ cagA-, and 2,984 (62.0%) were H. pylori-. The adjusted odds of being overweight were 1.17 (95% confidence interval: 0.98, 1.39; p = 0.075) for the H. pylori+ cagA+ group and 0.99 (95% confidence interval: 0.80, 1.22; p = 0.92) for the H. pylori+ cagA- group in comparison with H. pylori- subjects. Serum leptin levels did not differ significantly between the three H. pylori groups. In this US population-based study, there was no significant association between H. pylori colonization, cagA+ strains of H. pylori, and being overweight.