Hospital-based records from major cities of India, where roughly a quarter of the population resides, identified the frequency of neural tube defects (NTDs) as ranging from 3.9 to 8.8 per 1000 births, but the incidence in rural areas is unknown. We did a population-based door-to-door survey of mothers living in remote clusters of villages in Balrampur District in Uttar Pradesh, a region ranked as the least-developed area in India. The data showed that the incidence of NTDs was 6.57-8.21 per 1000 livebirths, which is among the highest worldwide. India's Ministry of Health needs to produce a strategy to reduce the incidence of such defects.