ABSTRACT: Background:Major birth defects increase the risk of fetal death and pediatric hospitalization, which also impact on healthcare costs. Sociodemographic factors can drastically affect reproductive health and be used to discriminate the exposure to hidden risk factors. Foz do Iguassu is a Brazilian city located in the triple-border region of Brazil / Paraguay / Argentina with high rates of birth defects. However no study aimed to verify factors associated with this incidence or preventive care is reported. The current work investigated the prevalence of major birth defects and its association with maternal sociodemographic factors in Foz do Iguassu. Methods:In this population-based cross-sectional study we used data of all live births occurred in Foz do Iguassu from 2012 to 2017. The associated sociodemographic variables such as maternal age, maternal education, maternal race, country of residence, maternal parity and onset of prenatal care were analyzed. Each major birth defect was described according to absolute and relative frequencies, Kruskal-Wallis and logistic regression models were used to evaluate variables associated with selected birth defects. Results:The most prevalent major birth defects were Cleft Lip and/or Palate (9.5/10,000), gastroschisis (6.93/10,000), spina bifida (5.53/10,000), hydrocephalus (5.53/10,000), hypospadias (4.55/10,000), Down syndrome (4.23/10,000), anencephaly (2.93/10,000), anorectal atresia / stenosis (1.95/10,000), undetermined sex (1.95/10,000), esophageal atresia / stenosis with or without fistula (1.63/10,000) and limb reduction defects (1.30/10,000). Maternal age was associated with gastroschisis and Down syndrome. Only maternal education up to 7?years was statistically associated with major birth defects considering all other sociodemographic variables. Conclusion:Cleft Lip and/or Palate and Gastroschisis prevalence were higher than those found in the literature. This findings may suggest a distinct epidemiological behavior regarding major birth defects in the region. The work opens new perspectives for birth defects risk factors in the triple-border.