Congenital Heart Disease (CHD) is one of the most common birth defects. It is the single most modifiable cause of infant mortality under one year of age. Therefore, the causes of CHD have been extensively researched in the past but the etiology remains largely unknown. Environmental risks, particularly maternal risk factors for congenital cardiac malformation have been evaluated in the original BWIS previously. However, in this research we examined one of the additional risk factors. We sought to determine whether maternal headache during six months prior to conception and throughout gestation until birth is a risk factor for CHD in the BWIS dataset. Among 3274 singleton cases and 3519 controls, a maternal report of headache was found to be associated with a nearly 20% increase in the risk of a congenital heart defect (OR= 1.2 p=0.001). Moreover, any medications use for headache 1-6 months prior to conception increased the risk of abnormal cardiac development by 1.3 fold (OR = 1.3, p=0.0004). Aspirin or aspirin containing analgesics were found to increase the risk for CHD at the defined risk period. According to subgroup analysis, aspirin or aspirin containing analgesics and acetaminophen or acetaminophen containing analgesics were found to be the risk factor for CTD i.e. Conotruncal defects. Furthermore, aspirin or aspirin containing analgesics increased the risk for PVSD i.e. Peri-membranous Ventricular Defect in offspring when the mother uses these drugs 1-6 months prior to conception. Additionally, the risk for CVD i.e. critical valve disease were found to be increased when women were exposed to aspirin or aspirin containing analgesics during third trimester after pregnancy. In conclusion, maternal headache increased the risk for CHD by 20% and the use of headache medications specifically pain relievers during 1-6 months prior to conception modulated type of defect was observed.