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Telomere length (TL) has been associated with age-related health outcomes. We investigated the relationship of TL with cardiometabolic risk profile in adult Americans. We used the National Health and Nutrition Examination Surveys for 1999 to 2002, accounting for complex sampling and survey design. Of the 8892 eligible participants, 47.8% (n = 4123) were men. Mean serum high-density lipoprotein cholesterol concentrations significantly increased across increasing TL quarters (P = .013), and mean fat mass, fat-free mass, hemoglobin A1c (HbA1c), and C-reactive protein significantly decreased across increasing TL quarters (all P < .001) in men. Only HbA1c levels significantly decreased across increasing TL quarters (P = .041) in women. Males in the upper quarter of TL had lower (38%) odds of prevalent metabolic syndrome compared with those in the lower quarter (P < .001). These results support the hypotheses that cardiometabolic factors are related to TL, especially in men.