Background: Early childhood caries (ECC) is a severe form of dental decay with multi-factorial origin. Objectives: The aim of this cross-sectional study was to determine the prevalence and related risk factors of ECC among preschool children residing in rural and urban areas of Trivandrum district in Kerala. Methods: A sample size of 1329 preschool children of <60 months of age was randomly selected from rural and urban areas of Trivandrum and decayed missing filled teeth indices were recorded. A standardized questionnaire was distributed to the parents. The data were subjected to SPSS version 16 and statistically analyzed with Chi-square test. Results: Prevalence of ECC in the study sample was found to be 54%. Furthermore, a positive association was obtained between ECC and age of the child, location of residence, dietary habits, and oral hygiene habits. Conclusion: There is an urgent need to implement preventive and curative oral health programs for preschool children in rural and urban areas.