Background The transport and logistics industry contributes to a significant proportion of the Australian economy. However, few studies have explored the economic and clinical burden attributed to poor truck driver health. We therefore estimated the work-related mortality burden among truck drivers over a 10-year period. Methods Dynamic life table modelling was used to simulate the follow-up of the Australian male working-age population (aged 15–65 years) over a 10-year period of follow-up (2021–2030). The model estimated the number of deaths occurring among the Australian working population, as well as deaths occurring for male truck drivers. Data from the Driving Health study and other published sources were used to inform work-related mortality and associated productivity loss, hospitalisations and medication costs, patient utilities and the value of statistical life year (VoSLY). All outcomes were discounted by 5% per annum. Results Over 10 years, poor truck driver health was associated with a loss of 21,173 years of life lived (discounted), or 18,294 QALYs (discounted). Healthcare costs amounted to AU$485 million (discounted) over this period. From a broader, societal perspective, a total cost of AU$2.6 billion (discounted) in lost productivity and AU$4.7 billion in lost years of life was estimated over a 10-year period. Scenario analyses supported the robustness of our findings. Conclusions The health and economic consequences of poor driver health are significant, and highlight the need for interventions to reduce the burden of work-related injury or disease for truck drivers and other transport workers.