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Objective Diesel engine exhaust (DEE) is a common occupational exposure associated with lung and bladder cancers and chronic respiratory and cardiovascular diseases. The association between DEE and lung cancer is well-established, but the relationship with other health outcomes is less understood. This study assesses potential dose-response relationships for lung and bladder cancers, chronic obstructive pulmonary disease (COPD), and ischemic heart disease (IHD) in Ontario workers exposed to DEE in the Occupational Disease Surveillance System (ODSS) using a new job-exposure matrix, the Diesel Exhaust in Canada Job-Exposure Matrix (DEC-JEM).Material and Methods The ODSS includes ~2.2 million workers identified through workers’ compensation claims (1983-2019). Workers were followed for cancer through linkage with the Ontario Cancer Registry (1983-2020). For COPD and IHD, the Discharge Abstract Database (2006-2020), National Ambulatory Care Reporting System (2006-2020), and Ontario Health Insurance Plan (1999-2020) were used. Exposure was assessed using DEC-JEM, a semi-quantitative job-exposure matrix based on expert assessment and published exposure data of measurements of elemental carbon. Cox-proportional hazards models were used to estimate hazard ratios and 95% confidence intervals, adjusted for age, birth year, and sex.Results Overall, 24,958 incident lung cancer, 8788 bladder cancer, 47,503 COPD, and 261,593 IHD cases were identified. Among exposed cases (all outcomes), the majority (90%) were assigned low exposure. Statistically significant increased risks of lung cancer (33%), bladder cancer (22%), COPD (33%), and IHD (15%) were observed among exposed workers compared to unexposed workers. Risk for all outcomes was notably higher among the high/very high group. The risk for females was generally higher than males, except for IHD. There was an increased risk for all diseases in transportation, manufacturing, and construction.Conclusion This study improved understanding of DEE health effects and could potentially improve workers compensation practices. Targeted prevention resources could reduce DEE exposure and occupational disease risk.