Purpose <p>This study explored the association between TPOAb levels and the incidence and progression of coronary artery calcification (CAC) among participants from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).</p> Methods <p>We included individuals with no prior cardiovascular disease who underwent two CAC measurements within the ELSA-Brasil cohort from the São Paulo Research Center. Fasting serum TPOAb levels were analyzed as continuous data, categorized in quartiles, and as detectable and positive levels. Incident CAC was defined as a baseline CAC = 0 followed by a CAC &gt; 0 in the second measurement. CAC progression was assessed using the Hokanson method only for participants with CAC &gt; 0 at baseline. We performed Poisson regression models with robust variance and logistic regression models using the first quartile of TPOAb as the reference.</p> Results <p>A total of 3013 individuals were included (57.2% women, age 49.3 ± 8.1 years, 55.2% white). The third (IRR = 1.38, 95% CI = 1.03–1.85) and the fourth (IRR = 1.43, 95% CI = 1.07–1.91) quartiles of TPOAb were associated with a higher risk of CAC incidence, even after adjusting for sociodemographic variables, cardiovascular risk factors, and thyroid function. These associations remained consistent in sensitivity analyses for euthyroid individuals (Q3: IRR = 1.49, 95% CI = 1.07–2.06 and Q4: IRR = 1.60, 95% CI = 1.15–2.22). Sex-stratified analyses revealed a stronger association between the fourth quartile of TPOAb and CAC incidence in men, while the third quartile was significantly associated with CAC incidence in women. There was a statistically significant association between high detectable TPOAb and CAC progression (OR = 1.50, 95% CI = 1.01–2.24).</p> Conclusion <p>Our findings indicate that individuals with higher levels of TPOAb were at higher risk of developing CAC over a 5-year follow-up period, suggesting an atherogenic role of TPOAb independent of thyroid function.</p>