Background <p>The Centers for Disease Control and Prevention (CDC) reports that water fluoridation is among the ten greatest public health achievements of the 20^th&#xa0;Century. Tooth decay (TD) prevention and neurodevelopmental disorder (ND) risk were assessed in relation to childhood water fluoridation exposure.</p> Methods <p>This longitudinal cohort study examined the Independent Healthcare Research Database (IHRD) composed of prospectively collected healthcare data from the Florida Medicaid system for the period 1990–2012, using logistic and frequency statistical modeling (with adjustment for covariates). A cohort of 73,254 children continuously enrolled for their first 10&#xa0;years of life was examined. The yearly percentage of persons in Florida receiving fluoridated water exposure from community water systems was examined by county. The number of children diagnosed with TD, autism spectrum disorder (ASD), attention deficit-hyperactivity disorder (ADHD), intellectual disability (ID), and specific delays in development (SDD) was evaluated.</p> Results <p>Fluoride exposure in the year of birth, statistically&#xa0;significantly and dose-dependently, slightly reduced the risk of TD, and, separately, slightly increased the risk of ASD, ADHD, ID, and SDD. During the first 10&#xa0;years of life, children who were fluoride-exposed as compared to unexposed were at significantly lower risk for TD, and, separately, at significantly greater risk for ASD, ID, and SDD.</p> Conclusions <p>Findings from the present study, coupled with previous studies, suggest new risk/benefit analyses of water fluoridation should be undertaken.</p>