Background: A higher dietary intake of carotenoid-rich foods and higher circulating concentrations of carotenoids have been associated with better lung function in cross-sectional studies; however, the longitudinal association between carotenoids and lung function has shown conflicting results. Objective: We examined the longitudinal association between serum carotenoids (β-cryptoxanthin, α-carotene, β-carotene, lutein/zeaxanthin, and lycopene) and the evolution of lung function. Design: We evaluated our hypothesis in the Coronary Artery Risk Development in Young Adults (CARDIA) prospective cohort study. Spirometry testing was conducted at year 0 (1985-1986) and at follow-up in years 2, 5, 10, and 20; serum carotenoids were assayed at years 0 and 15, and diet was assessed at years 0 and 20. Results: Year 0 sum of provitamin A carotenoids and β-cryptoxanthin concentrations were associated with maximum forced vital capacity (FVC) (P ≤ 0.01) and forced expiratory volume in 1 s (FEV 1) (P ≤ 0.05) (maximum across years 0-10) in linear regression models adjusted for age, race, height, study center, amount of physical activity, smoking status, and BMI. Year 0 lutein/zeaxanthin and lycopene were not associated with maximum lung function. Baseline concentrations of lutein/zeaxanthin, lycopene, sum of the 3 provitamin A carotenoids, β-carotene, and β-cryptoxanthin were each inversely associated with a decline from maximum FVC and FEV 1 (P ≤ 0.04). The sum of provitamin A carotenoids and lycopene remained significant after adjustment for dietary intake related to serum carotenoids (P ≤ 0.03). The 15-y change in provitamin A carotenoid and lutein/zeaxanthin concentrations was associated with a slower decline from maximum FVC and FEV 1 (P ≤ 0.04). Conclusion: These findings support an association between serum carotenoid concentrations and a decline in lung function.