Leucocyte telomere length (LTL) has been reported to be linked to ageing, cancer and cardiovascular disease (cVD). this study aimed to explore the association between LtL and cVD risk in a nationally representative sample of U.S. adults. Complex associations, including nonlinearity and interaction, were also examined. A total of 7,378 subjects from the National Health and Nutrition Examination Survey (NHANES) 1999-2002 were collected. Telomere length was detected from DNA samples and expressed as the mean t/S ratio (telomere repeats per single-copy gene). We performed multiple logistic regression models and interactive analysis to explore the associations between LtL and cVD risk by adjusting for potential confounders. We also performed a sensitivity analysis to investigate the robustness of our results. Among all participants, LTL was associated with the risk of CVD (OR = 0.79, 95% CI: 0.63~0.98, P = 0.033) in a linear manner rather than in a nonlinear manner (P = 0.874). Interaction effects of LTL with both education (P = 0.017) and hypertension (P = 0.007) were observed. Furthermore, using subgroup analyses, protective effects of LTL on CVD risk were found in females and in individuals who were college graduates or above, had serum cotinine >10 ng/ml, did not have hypertension, or had normal white blood cell levels. LTL is linearly inversely associated with CVD risk in the general population of the United States. Telomeres are repetitive sequences of nucleotides at the ends of chromosomes that play a role in the maintenance of genic integrity. Telomeres are involved in many physiological processes 1 such as cell senescence 2 and endometrial regeneration 3. Leucocyte telomere length (LTL) is the longest at birth and decreases with age 4. Moreover, the shortening of LTL affects the progression of diseases, including ageing 5,6 , immune dysfunction 7 , post-traumatic stress disorder 8 , diabetes 9 , cardiovascular disease (CVD) 10 , and cancer 5,11. CVD refers to heart and blood vessel abnormalities and is one of the most common causes of noncommunicable disease mortality 12 , accounting for approximately 17.5 million deaths worldwide 13. The United States has the largest number of CVD patients in the world 14. Reportedly, approximately 1,500,000 U.S. adults are affected by CVD each year 15 , and millions of Americans have CVD risk factors 16. Peng et al. found that longer LTL was associated with cardiovascular health (CVH) indices (i.e., a surrogate measure of CVD risk) in American Indians 17. Similarly, Gebreab et al. explored the associations between LTL and CVH and observed similar results in the general U.S. population, especially in females and non-Hispanic whites 18. Another report showed an inverse association between LTL and coronary artery calcification in African Americans 19. A meta-analysis reported an inverse association between LTL and the risk of CVD 10. However, among the general U.S. population, the association between LTL and the risk of CVD remains unclear. In addition, people of different eth...