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Background: Cardiac anomalies are the most prevalent congenital malformations among live births in the world. In Brazil, it is estimated that nearly 25,757 new cases occur each year, and the Southeast region presents the highest prevalence, with 10 new cases/1,000 live births. Objective:The aim of this study is to evaluate the epidemiology of congenital heart disease (CHD) in the state of São Paulo.Methods: This is a cross-sectional and time-series observational study with data from the Brazilian Information System on Live Births. Heart-related cardiac malformation cases -International Classification of Diseases (ICD) 10th revision Q20.0 to Q24.9 -were selected from January 2010 to December 2018, in the state of São Paulo, Brazil. This study analyzed rates of malformations per year and investigated associated factors, using single and multiple logistic regression models. The significance level adopted in this study was 5%. Results:The highest cardiac malformation rate was in the São Paulo metropolitan region (2.84:1000), while the lowest was found in the region of Franca (0.3:1000). The most frequent defect was interatrial communication (38.2%). The main associated factors observed in this study were prematurity of 22 to 27 weeks (OR=4,401 95% CI: 3,796-5,104