BACKGROUND: The aim of this study is to investigate the association between socio-occupational status and the frequency of major congenital anomalies in offspring. METHODS: The study population comprised 81 435 live singletons born to mothers enrolled in the Danish National Birth Cohort between 1996 and 2002. A total of 3352 cases of major congenital anomalies (EUROCAT criteria) were identified by linkage to the National Hospital Discharge Register. Malformations were recorded at birth or in the first year of life. Information about maternal and paternal socio-occupational status was collected prospectively using telephone interviews in the second trimester of pregnancy and was categorized as high, middle or low. Associations were measured as relative prevalence ratios using the highest socio-occupational status within the couple as the reference group. RESULTS: The prevalence of all recorded major congenital anomalies was similar, about 4%, in all the socio-occupational categories. Low social status of the couple did, however, correlate with a higher prevalence of congenital anomalies of the 'respiratory system'. No association was substantially attenuated when we adjusted for maternal and paternal age, smoking status, maternal alcohol habits, folic acid intake and body mass index. When malformations of the heart and the cardiovascular system were grouped together, they were more frequent in families where both parents presented a low socio-occupational status. CONCLUSION: We detected an association between low socio-occupational status and congenital anomalies of the respiratory system, the heart and the circulatory system. These malformations are good candidates for a large study on occupational, environmental and social determinants.