The purpose of this study was to determine the independent effects of waist circumference (WC) and physical inactivity on the risk of mortality in women. This prospective cohort study included 5421 female participants 20-69 years of age in the 1981 Canada Fitness Survey. WC was measured with an anthropometric tape and leisure-time physical activity levels over the previous 12 months were assessed with a questionnaire. Mortality surveillance was conducted by data linkage with the Canadian Mortality Database through 31 December, 1993. The hazard ratios (HR) of mortality were estimated using Cox proportional hazards regression with age, smoking status, and alcohol consumption included as covariates in all models. A total of 225 deaths occurred over an average of 12.4 years of follow up (67 500 person-years of follow up). Physical activity (HR = 0.78; 95% C.I.: 0.64-0.95) and WC (HR = 1.17; 95% C.I.: 1.05-1.31) were associated with mortality when included in separate regression models. When included in the same model, both physical activity (HR = 0.79; 95% CI: 0.65-0.96) and WC (HR = 1.16; 95% C.I.: 1.04-1.30) remained independent significant predictors of mortality. In conclusion, physical inactivity and high WC have significant independent risks of premature mortality among women.