Systematic reviews produce conflicting conclusions regarding dental caries-preventive effects of water fluoridation in adults. The authors investigated the relationship using data from the nationally representative 2004-2006 Australian National Survey of Adult Oral Health. Effects were compared between the pre-fluoridation cohort born before 1960 (n = 2,270) and the cohort born between 1960 and 1990 (n = 1,509), when widespread implementation of fluoridation increased population coverage from < 1% to 67%. Residential history questionnaires determined the percentage of each person's lifetime exposed to fluoridated water. Examiners recorded decayed, missing, and filled teeth (DMF-Teeth) and decayed and filled tooth surfaces (DF-Surfaces). Socio-demographic and preventive dental behaviors were included in multivariable least-squares regression models adjusted for potential confounding. In fully adjusted models, > 75% of lifetime exposure to fluoridation relative to < 25% of lifetime exposure was associated with 11% and 10% fewer DMF-Teeth in the pre-1960 (p < .0001) and 1960-1990 cohorts (p = .018), respectively. Corresponding reductions in DF-Surfaces were 30% (p < .001) and 21% (p < .001). Findings for intermediate fluoridation exposure suggested a dose-response relationship. Results were consistent in sensitivity analyses accounting for missing data. In this nationally representative sample of Australian adults, caries-preventive effects of water fluoridation were at least as great in adults born before widespread implementation of fluoridation as after widespread implementation of fluoridation.