In this study, we aimed to explore regional differences in maternal lifestyle during pregnancy related to congenital heart defects (CHD) in Shaanxi province, Northwestern China. A large-scale epidemiologic survey of birth defects among infants born during 2010-2013, was conducted in Shaanxi province. Non-spatial and geographic weighted logistic regression models were used for analysis. The spatial model indicated that passive smoking frequency was positively associated with CHD for 43.3% of participants (P < 0.05), with the highest OR in North Shaanxi and the lowest in South Shaanxi. Approximately 49.2% of all mothers who ever drink tea were more likely to have an infant with CHD (P < 0.05), with the highest OR values observed in North and Central Shaanxi. Additionally, maternal alcohol intake frequency ≥ 1/week was significantly correlated with CHD among about 24.7% of participants (P < 0.05), with OR values ranging from 0.738 (Central Shaanxi) to 1.198 (North Shaanxi). The rates of unhealthy maternal lifestyles during pregnancy associated with CHD differed in various areas of the province. The role of geographical variations in these factors may provide some possible clues and basis for tailoring site-specific intervention strategies.