Background: The aim of the present study was to clarify the association between waist circumference and all-cause and cardiovascular disease (CVD) mortality risk in relatively lean Japanese subjects. Methods and Results: A total of 3,554 men and 4,472 women who had no history of CVD were examined and their waist circumference measured at baseline. The subjects were aged ≥40 years and were obtained from 3 prospective cohort studies during 1988–1996. Hazard ratios for all-cause and CVD mortality were analyzed over a follow-up period of 14.7 years using a Cox proportional hazards model and penalized spline method, after adjustment for study cohort, age, smoking, alcohol drinking, hypertension, dyslipidemia, and diabetes. Compared with the lowest quintile, the highest quintile of waist circumference in men was associated with a linear reduction in all-cause mortality risk (multivariate-adjusted hazard ratio, 0.73; 95% confidence interval: 0.60–0.89; P for trend=0.001). CVD mortality risk was increased in men aged ≤65 years with a higher waist circumference. This relationship was U-shaped. Waist circumference was not associated with all-cause or CVD mortality risk in women. Conclusions: Waist circumference was associated inversely with increased risk of all-cause death in men, but not in women. Middle-aged men with a greater waist circumference potentially have an increased risk of CVD mortality.  (Circ J 2012; 76: 2867–2874)