Bilirubin is a potent antioxidant, and serum total bilirubin (TB) is reported to be negatively associated with cardiovascular disease (CVD). There has been no report on the association between TB and CVD prevalence in Japanese. The aim of the study is to examine the association between TB and CVD prevalence in a Japanese health screening population. Prevalence of CVD was studied in 3,375 Japanese men and 2,069 Japanese women. Odds ratios (ORs) of each higher quintile of TB using the lowest quintile as the reference in men and of each higher tertile of TB using the lowest tertile as the reference in women were calculated for coronary heart disease (CHD) and stroke adjusting for age, liver function tests, smoking, physical activity, and alcohol consumption. The ORs [95% confidence intervals (CIs)] for CHD and stroke of the 2nd, 3rd, 4th, and 5th quintiles of TB were 0.63 (0.37–1.07) and 0.49 (0.24–1.00), 0.45 (0.22–0.90) and 0.65 (0.28–1.51), 0.69 (0.39–1.20) and 0.37 (0.15–0.87), and 0.61 (0.34–1.09) and 0.40 (0.18–0.92), respectively in men. The ORs (95% CIs) for CHD and stroke of the 2nd and 3rd tertiles of TB were 0.63 (0.37–1.07) and 0.49 (0.24–1.00), and 0.61 (0.34–1.09) and 0.40 (0.18–0.92), respectively in women. Low TB was associated with the higher prevalence of CHD and stroke in men and with the higher prevalence of stroke in women among a Japanese health screening population.