Comparative, cross-jurisdictional research has the potential to increase our understanding of the causes of work injury and disease and identification of effective prevention and return-to-work policies. Results from comparative research may be more powerful than those from single jurisdiction studies as we are able to control for additional sources of variation that may be driving the results and take advantage of policy and program variation across jurisdictions to identify natural experiments that enable stronger causal inference to be drawn. Single jurisdiction studies attempt to do this using variation over time, but often temporal variation is confounded by other factors or is too small for there to be meaningful inference. While the comparative research approach can be powerful, careful attention needs to be paid to the development of comparable study populations and measures and to understanding the differences and/or comparability of the policies under study. Sources of variations across jurisdictions that could lead to spurious differences in the policy outcome need to be identified and controlled for. Fundamentally this implies the need to study the same population at risk, ensuring that cohorts, measures and outcomes are comparable, as well as accounting for other structural or contextual factors that could affect outcomes across jurisdictions. This synthetic presentation will exemplify these challenges with reference to claims and injury data drawn from the Canadian province of British Columbia and the Australian state of Victoria and in comparing claim rates and return-to-work outcomes in cohorts of workers employed in similar occupations and industries. The presentation concludes with a brief overview of a nascent international collaboration that has the aim of creating a network of researchers and data to conduct comparative, cross-jurisdictional occupational health and safety and workers’ compensation research in jurisdictions from Oceania, North America and Europe.