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The study aimed to explore the prospective associations between psychosocial factors at work from the job strain model and preventable mortality, including smoking- and alcohol-related mortality as well as external causes of death. The study was based on prospective data and relied on a sample of 1,511,456 individuals for which data on job history, mortality and causes of death were linked over the 1976-2002 period. Exposures were the factors from the job strain model imputed through a job-exposure matrix. Various time-varying measures of exposure were used including current exposure and two measures of cumulative exposure. Preventable mortality was defined using the OECD/Eurostat list of preventable causes of death. The associations between exposures and outcomes were studied using Cox proportional hazards models. Effect modification by gender was also assessed. Over the study period, 57,264 preventable deaths occurred before the age of 75 years. Low decision latitude, low social support, job strain, iso-strain, passive job, and high strain were associated with preventable mortality, and associations of stronger magnitude were found for job strain and isostrain among men. Stronger associations were observed for alcohol-related mortality than for smoking-related mortality and external causes of death. The fractions of preventable mortality attributable to current exposure to job strain and isostrain were significant among men only (5.1% and 3.3%). Psychosocial factors at work from the job strain model may play a role on preventable mortality. Intensifying research and prevention towards the psychosocial work environment may be helpful to reduce risky health-related behaviours and related mortality., (Copyright © 2020 Elsevier Inc. All rights reserved.)