Here we report the results of prenatal diagnosis at the Hospital Universitario Ramón y Cajal since its opening in 1979 to 2010, establishing a parallelism between the different methodologies for screening and prenatal diagnosis, clinical indications, and demographic changes. It shows how the indications have varied as to the structure of the population did. These changes have been possible thanks to the fact that the screening and prenatal diagnosis methods have allowed it. Demonstrating, once again, how procedures evolve with technology and adapt to the demography. This evolution has allowed to make a more effective prenatal diagnosis because the clinical indications have been more precise what has allowed to detect the same number of fetuses with chromosomal abnormalities by performing less invasive procedures, which has led to an optimization of prenatal diagnosis saving resources and personnel and, above all, avoiding unnecessary fetal losses.