Background: The impact of enamel defects of the first permanent molars on caries experience and child oral health-related quality of life was evaluated in a cohort study. Methods: Children who participated in a study of enamel defects of the first permanent molars 8 years earlier were invited for a follow-up assessment. Consenting children completed the Child Perception Questionnaire and the faces Modified Child Dental Anxiety Scale, and were examined by two calibrated examiners. ANOVA, Kruskal-Wallis, negative binomial and logistic regression were used for data analyses. Results: One hundred and eleven children returned a completed questionnaire and 91 were clinically examined. Negative binomial regression found that oral health impacts were associated with gender (boys, risk ratio (RR) = 0.73, P = 0.03) and decayed, missing or filled permanent teeth (DMFT) (RR = 1.1, P = 0.04). The mean DMFT of children were sound (0.9, standard deviation (SD) = 1.4), diffuse defects (0.8, SD = 1.7), demarcated defects (1.5, SD = 1.4) and pit defects (1.3, SD = 2.3) (Kruskal-Wallis, P = 0.05). Logistic regression of first permanent molar caries found higher odds of caries experience with baseline primary tooth caries experience (odds ratio (OR) = 1.5, P = 0.01), the number of teeth affected by enamel defects (OR = 1.9, P = 0.05) and lower odds with the presence of diffuse enamel defects (OR = 0.1, P = 0.04). Conclusions: The presence of diffuse enamel defects was associated with lower odds of caries experience.