BackgroundHeterotaxy syndrome (HTX) is a constellation of defects including abnormal organ lateralization and often including congenital heart defects. HTX has widely divergent population‐based estimates of prevalence, racial and ethnic predominance, and mortality in current literature.MethodsThe objective of this study was to use a population‐based registry to investigate potential racial and ethnic disparities in HTX. Using the Texas Birth Defects Registry, we described clinical features and mortality of HTX among infants delivered from 1999 to 2006. We calculated birth prevalence and crude prevalence (cPR) ratios for infant sex, maternal diabetes, and sociodemographic factors.ResultsA total of 353 HTX cases were identified from 2,993,604 births (prevalence ratio = 1.18 per 10,000 live births. HTX prevalence was approximately 70% higher among infants of Hispanic and non‐Hispanic black mothers and 28% higher among female infants (cPR = 1.28; 95% confidence interval,1.04–1.59). There was a twofold higher female preponderance for infants of mothers who were non‐Hispanic white or black. Mothers with diabetes were three times more likely to have a child with HTX compared with nondiabetics (cPR = 3.13; 95% confidence interval, 2.12–4.45). Among nondiabetics, HTX cases were 86% more likely to have a Hispanic mother and 72% a non‐Hispanic black mother. First‐year mortality for live born children with HTX was 30.9%.ConclusionThis study represents one of the largest population‐based studies of HTX to date, with a novel finding of higher rates of HTX among Hispanic infants of mostly Mexican origin, as well as among female infants of only non‐Hispanic white and black mothers. These findings warrant further investigation.Birth Defects Research (Part A), 2015. © 2015 Wiley Periodicals, Inc. Birth Defects Research (Part A) 103:941–950, 2015. © 2015 Wiley Periodicals, Inc.