The objective of this study was to determine the association between parental cigarette smoking and the risk of congenital heart septal defects in Kaunas infant population in 1995–2005. Material and methods. An epidemiological case-control study was conducted. The study comprised 261 newborns with congenital heart septal defects (cases) and 1122 randomly selected newborns without any defects (controls), born in Kaunas city during 1995–2005. Information on potential risk factors of newborns’ health was collected through an interview with parents using standardized questionnaires. Multivariate logistic regression analysis was used to assess the association between parental smoking and septal defects while controlling for possible confounders. Results. According to the validated registry, 371 newborns with congenital heart malformations were born in Kaunas city during 1995–2005; 70.3% of cases had ventricular and/or atrial septal defects. After adjustment for possible confounding factors – maternal education, social status, marital status – a statistically significant relationship was observed between parental smoking and congenital heart septal defects. Parental, maternal, and paternal smoking was significantly associated with a 2.27-fold (adjusted OR=2.27; 95% CI, 1.49–3.46), 2.2-fold (adjusted OR=2.20; 95% CI, 1.01–4.79), and 1.45-fold (adjusted OR=1.45; 95% CI, 1.03–2.03) increased risk of defects if compared with nonsmoking parents. Conclusions. According to the results of our study, parental smoking was significantly associated with an increased risk of congenital heart septal defects in infants.