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Objective The occupational exposome, encompassing a wide range of work exposures, may impact cardiovascular disease risk. However, most evidence is insufficient and does not account for co-exposures. Thus, the primary objective of this study is to investigate the contribution of occupational exposures in relation to ischemic heart disease (IHD), including myocardial infarction (MI), and stroke.Material and Methods Five cohorts were included: the Danish Occupational Cohort with Exposure Data (DOC*X), the State of Labor Force in Finland (SLFF) cohort, Lifelines from The Netherlands, Nor-Work from Norway, and the Swedish National Cohort on Work and Health (SNOW). Yearly occupational data were linked to the European Job-Exposure Matrix (EuroJEM) to assign exposure to diesel engine exhaust, respirable crystalline silica dust, wood dust, fast breathing and heavy lifting due to physical workload, noise, low decision authority, and solar UV radiation. Discrete-time hazard models were created to investigate the impact of exposure in the previous year, and a 10-year cumulative exposure, on the risk of IHD and stroke, adjusting for age, gender, education, marital status, country of origin, and other occupational exposures.Results Preliminary results from SNOW show that after adjusting for other occupational exposures, noise and physical workload were associated with increased risk of IHD, MI, and stroke. Diesel engine exhaust was associated with an increased risk of MI only. Analyses on cumulative exposure are ongoing. Results from all cohorts will be summarized in a meta-analysis.Conclusion This study will be the first multi-national study to investigate the impact of several occupational exposures on IHD and stroke. Our findings are expected to contribute to a deeper understanding and characterization of these complex relationships.Funding This work is part of the Exposome Project for Health and Occupational Research (EPHOR), funded by the European Union’s Horizon 2020 research and innovation programme, grant agreement No 874703.