Background Several studies have suggested that the exposure to cadmium （Cd） increased mortalities from renal diseases, cardiovascular diseases and malignant neoplasm, including lung cancer and prostate cancer among inhabitants living in Cd-polluted areas and factory workers. This study aimed to assess the influence of environmental exposure to Cd on long term outcome of inhabitants living in an area polluted by Cd. Methods A 22-year follow-up study was conducted with 3119 inhabitants （1403 men and 1716 women） living in the Cd polluted Kakehashi River basin in Japan. The subjects were divided into 4 groups according to the amount of urinary Cd level （〈3.0 μg/g creatinine （Cr）, 3.0-4.9 μg/g Cr, 5.0-9.9 μg/g Cr, and -〉10.0 μg/g Cr）. Mortality was calculated by the person-years method. Hazards ratios （HR） and 95% confidence intervals （CI） were assessed by the Cox＇s proportional hazard model. Results Compared with urinary Cd 〈3.0 μg/g Cr group, the HR of 5.0-9.9μg/g Cr and 〉10.0 μg/g Cr groups were significantly increased after adjustment for age in both sexes： 1.24 （95% Cl 1.01-1.51） and 1.48 （95% CI 1.17-1.90） for men; 1.64 （95% CI 1.17-2.28） and 1.78 （95% Cl 1.27-2.50） for women. The most frequent cause of death was malignant neoplasm in men and cardiovascular diseases in women. The significant increase in mortality risk for cardiovascular diseases was observed in the subjects with 〉10 μg/g Cr in both sexes： 1.79 for men （95% Cl 1.02-3.12） and 2.38 for women （95% Cl 1.11-5.07）. When the subjects were divided into 2 categories （〈20μg/g Cr and 〉20 μg/g Cr）, the HR of the urinary Cd 〉20 μg/g Cr group for nephritis and nephrosis were 4.82 （95% Cl 1.07-21.61） in men and 7.92 （95% Cl 1.77-35.33） in women, respectively. The significant increase was not observed for malignant neoplasm. Conclusion These results suggest a dose-response relationship between Cd body burden and mortality for cardiovascular diseases, cerebrovascular diseases and nephritis and nephrosis.