The aim of our project was to study possible etiological factors in the origin of congenital heart defects (CHDs) because in the majority of patients the underlying causes are unclear. Cases with different CHD entities as homogeneously as possible were planned for evaluation in the population-based large data set of the Hungarian Case Control Surveillance of Congenital Abnormalities. Dead or surgically corrected 302 live-born cases with different types of left-ventricular outflow tract obstructive defects (LVOT, i.e., valvular aortic stenosis 76, hypoplastic left heart syndrome 76, coarctation of the aorta 113, and other congenital anomalies of aorta 32) were compared with 469 matched controls, 38,151 controls without any defects, and 20,750 malformed controls with other isolated defects. Medically recorded pregnancy complications and chronic diseases were evaluated based on prenatal maternity logbooks, whereas acute diseases, drug treatments, and folic acid/multivitamin supplementation were analyzed both on the basis of retrospective maternal information and medical records. The results of the study showed the role of maternal diabetes in the origin of LVOT in general, while panic disorder was associated with a higher risk of hypoplastic left heart syndrome and ampicillin treatment with a higher risk of coarctation of the aorta (COA). High doses of folic acid had a protective effect regarding the manifestation of LVOT, particularly COA. In conclusion, only a minor portion of causes was shown in our study; thus, further studies are needed to understand better the underlying causal factors in the origin of LVOT.