Since 1981, the Paris Congenital Malformations Registry has been recording cases of congenital malformations and chromosomal abnormalities in the Parisian population (approximately 38,000 births annually). The registry’s objectives are to conduct continuous surveillance of congenital anomalies in the covered area and to carry out research projects and population-based evaluations of public health measures. In this article, we summarize our work on the surveillance of congenital anomalies and our previous specific studies on the prenatal diagnosis of trisomy 21 as well as on the long-term outcomes of children with heart defects. A total of 30,510 cases of congenital anomalies (3.3% of births) were recorded during the 1981–2005 period, including 22,490 live births (2.4% of live births). The percentage of cases with a prenatal diagnosis rose sharply during this period, increasing from 16.2% of all cases of malformations in 1983 (the first year of data collection on prenatal diagnosis) to 69.1% in 2005. With regard to trisomy 21, the proportion of cases detected prenatally in women under 38 years of age increased ninefold, rising from 9.5% in 1983 to 84.9% in 2000. This percentage, as well as the prevalence of live births with trisomy 21 (an average of 7.1 per 10,000 births), tended to stabilize during the period from 2001 to 2005. For children with heart defects, we conducted research on trends in prenatal diagnosis, pregnancy terminations, and perinatal mortality using registry data from the 1981–2000 period. We continued this research by establishing a large population-based cohort of children with congenital heart disease who will be followed until the age of three. The follow-up includes data on mortality, cardiac and general morbidity, as well as psychomotor development using standardized instruments.