Background: There is an urgent need to assess the impact, on the incidence of neural tube defects, of the recently implanted flour fortification with folic acid in Chile. The Collaborative Study of Congenital Malformations in Latin America (ECLAMC) has carried out an uninterrupted register of congenital malformations in the last thirty years Aim: To assess the epidemiology of neural tube defects in Chile and determine the most adequate base period to evaluate the effects of Folic acid fortification. Material and methods: analysis of ECLAMC database that has registered all births over 500 g from 1967. Results: From 1967 to 1999, there were 434.624 births in 18 hospitals in Chile and 3.586.569 births in 155 hospitals in the rest of Latin America. The rate of neural tube defects in Chile was 17.03 per 10.000, significantly higher than the rest of ECLAMC (14.88 per 10.000). The prevalence of neural tube defects has a statistically significant secular tendency to increase in the study period and is higher among stillbirths, newborns with a birth weight of less than 1500 g, women and offspring of mothers aged less than 19 years old. Conclusions: The period 1982-1999 is considered the best period for reference comparisons of the effects folic acid supplementation (Rev Méd Chile 2001; 129: 531-9)