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<b><i>Background:</i></b> Intellectual disability (ID), characterized by impairments in intellectual function and adaptive behavior, affects 1-3% of the population. Many studies investigated its etiology, but few are cohort studies in middle-income countries. <b><i>Aims:</i></b> To estimate prevalence, etiology, and factors related to ID among children prospectively followed since birth in a Southern Brazilian city (Pelotas). <b><i>Methods:</i></b> In 2004, maternity hospitals were visited daily and births were identified. Live-born infants (n = 4,231) whose family lived in the urban area have been followed for several years. At the age of 2 and 4 years, performances in development and intelligence tests were evaluated using the Battelle Developmental Inventory and Wechsler Intelligence Scale, respectively. Children considered as having developmental delay were invited to attend a genetic evaluation. <b><i>Results:</i></b> At 4 years of age, the prevalence of ID was 4.5%, and the etiology was classified into 5 groups: environmental (44.4%), genetic (20.5%), idiopathic (12.6%), neonatal sequelae (13.2%), other diseases (9.3%). Most children presented impairment in two or more areas of adaptive behavior. There was no difference in prenatal care attendance or maternal schooling among the groups. <b><i>Conclusion:</i></b> For about 40% of children, ID was attributed to nonbiological factors, suggesting that the rate may be reduced with appropriate interventions early in life.