ABSTRACT Cardiovascular disease (CVD, including heart disease and stroke) is the leading cause of death worldwide and in the United States (U.S.), accounting for 2.8 million deaths in 2018 alone and with a prevalence nearing 50%.1,2 Related to this are long working hours, which remain quite high in the U.S. when compared to other countries.3,4 Recently, a series of systematic reviews and meta-analyses have identified a robust and dose-dependent relationship between long working hours and CVD.5–9 These reviews reported that working more than 55 hours a week was associated with a higher risk of CVD mortality in the European workforce. However, this association has not yet been systematically investigated in U.S. working populations, constituting a critical research gap that demands address. Our objective is to conduct secondary data analysis, in response to PAR-18-798, to better understand the relationship between long working hours and CVD mortality risk in the U.S., using data obtained from the National Health Interview Survey (NHIS) series of studies. The NHIS is an annually updated, large, nationally representative, and rich dataset featuring detailed information on demographics, working conditions, and health and disease status. The NHIS dataset represents a premiere opportunity to investigate the contribution of long working hours to excess CVD mortality. We propose to use the NHIS sample data from 1997- 2014 and the NHIS mortality data up to 2015 to examine associations between long working hours and CVD mortality, with a cumulative total of 18 years of follow-up. Our specific aims are to (1) investigate associations of long working hours with total CVD mortality; (2) investigate associations of long working hours with heart disease mortality as well as stroke mortality; and (3) test effect modification of demographic status (age, sex, race, region, and socioeconomic status (SES)) in the associations of long working hours with total CVD mortality, heart disease mortality, and stroke mortality, respectively. We hypothesize a dose-response relationship between long working hours and CVD mortality amongst the U.S. working population, and that this association will be modified by social and demographic characteristics. Our expected outputs and outcomes in the intermediate term anticipate the successful achievement of the specific aims, constituting the provision of high-quality, robust scientific evidence assessing the association of long working hours to CVD mortality in the U.S. This project has national and global relevance, and addresses goals set by the National Occupational Research Agenda (NORA) Health Work Design and Well-being sector and the NORA Cancer, Reproductive, Cardiovascular, and Other Chronic Disease Prevention cross-sectors. The ultimate long-term societal impact and contribution of this project would be to leverage such data to shape and inform interventional policy directives related to the limitation of working hours for th...