Background and aims: Abdominal aortic calcification (AAC) has been recognized as an independent predictor of cardiovascular disease (CVD) incidence and mortality. The aim of this cross-sectional study is to investigate the relationship between serum a-Klotho, an anti-aging hormone, and severe AAC in United States (US) civilians, which was not documented before. Methods and results: The data were obtained from the 2013-2014 National Health and Nutrition Examination Survey (NHANES), which included 2267 individuals aged 40-79 years. Serum aKlotho concentration, categorized into four quartiles, was examined by enzyme linked immunosorbent assay (ELISA). AAC was quantified by the Kauppila score system based on dual-energy Xray absorptiometry. The association between serum a-Klotho and severe AAC was determined by multivariable logistic regression models. After adjusting for multiple covariates, the odds ratios (OR) (95% CI) of severe AAC for participants in serum a-Klotho quartiles 2-4 were 0.83 (0.52, 1.32), 0.56 (0.34, 0.94), and 0.54 (0.32, 0.92), respectively, compared with those in quartile 1 (P for trend Z 0.007). The association between serum a-Klotho and severe AAC was stable in the different subgroups (all P for interaction>0.05). Conclusion: In a sample of US adults, serum a-Klotho levels were negatively related to the risk of severe AAC. Our findings indicated that serum a-Klotho may become a promising tool to predict the incidence and prognosis of CVD.(c) 2022 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.