This study sought to investigate the relationship between sitting time in main activities and all-cause, cardiovascular disease and cancer mortality. In 17,013 Canadians (18-90 years old) followed for an average of 12 years, there was a progressively higher risk of mortality across higher levels of sitting time from all-cause mortality and cardiovascular disease mortality but not cancer mortality. There was also a dose-dependent relationship (which was similar among physically inactive and active subjects) between daily sitting time and mortality rates among nonsmokers, former smokers and current smokers and across body mass index categories.