BACKGROUND. Literature conflicts regarding dental caries risk in cystic fibrosis (CF) relative to controls. METHODS. Prospective, observational study of age-related heterogeneity in caries rates and potential risk factors in CF patients ages 6–20 at a single clinic in Washington state (N=85). Caries rates for enrolled CF participants and historical controls from NHANES were compared using cubic spline regression models. Generalized linear regression models identified correlates of age and caries within CF. RESULTS. Children ages 6–9 with CF had significantly lower caries than controls (Holm’s P0.05). Eight biological/intraoral, medical, and behavioral factors were associated with caries and age in CF. CONCLUSIONS. Younger children with CF may be protected from caries, but there is apparent loss of protection in early adolescence associated with multiple risk factors. Additional research is needed to elucidate the oral-systemic relationship in individuals with CF.