Most childhood disabilities are caused by congenital factors such as birth defects. The present study aims to evaluate the effect of periconceptional nutrition intervention on the prevention of congenital disability among Chinese children using the National Birth Defects Intervention Project as a natural experiment. We obtained individual-level data from the Second National Sample Survey on Disability, a nationally representative survey, and 110 365 children born between September 1999 and August 2003 were included for analysis. Difference-in-differences estimates of the project effects on congenital disability were captured by exploiting temporal variation in the timing of project exposure across four birth cohorts along with geographical variation in project category at the province level. The findings contribute to an emerging body of evidence showing that prenatal micronutrient intervention before and during early pregnancy could substantially reduce the risk of congenital disability in childhood (OR 0·73; 95 % CI 0·57, 0·94). The National Birth Defects Intervention Project improved the awareness of reproductive health and disability prevention in the population. It highlights the need for a potential policy change focusing on early-life health investment in China.