Objective: Observational epidemiologic studies have shown that a high intake of dietary and high serum levels ofcarotenoids are associated with a reduced risk of mortality from cancer and cardiovascular disease. To investigatewhether high serum levels of carotenoids can reduce mortality rates, a population-based follow-up study was conductedamong Japanese inhabitants. Materials and Methods: Three thousand two hundred and fifty-four subjects (1,260males and 1,994 females) aged from 39 to 85 years who had attended health check-up programs from 1989 to 1995were recruited from the Japanese population. Serum levels of carotenoids, retinol and tocopherols were separatelydetermined by high-performance liquid chromatography. Hazard ratios for serum values of carotenoids, retinol andtocopherols were estimated by Cox’s proportional hazard model after adjusting for sex, age, and other confoundingfactors. Results: During the 11.7-year follow-up period, 140 deaths (86 males and 54 females) from cancer of all siteswere identified among the cohort subjects, including 41 from lung , 17 from stomach , 16 from colorectal and 12from liver cancer, as well as 89 deaths from cardiovascular disease, including 45 from heart disease and 37 fromstroke. High serum values of carotenoids including xanthophylls were apparently associated with low hazard ratiosfor mortality rates of cancer of all sites or of cardiovascular disease. High serum values of β-carotene, total carotene,provitamin A and total carotenoid for colorectal cancer or stroke also appeared to be related to low hazard ratios.Those of retinol and tocopherols were not associated with any reduction in risk of mortality from cancer orcardiovascular disease. Conclusions: Our follow-up study demonstrated that a typical Japanese diet related to elevatingserum levels of carotenoids with provitamin A activity may significantly reduce risk of mortality from cancer ofcertain sites or cardiovascular disease, especially colorectal cancer or stroke, while high serum levels of somexanthophylls, retinol and tocopherols do not.