Background: Canada continues to experience a national overdose crisis. While studies are available at the regional and provincial/territorial (P/T) levels, detailed national data regarding the burden and context of substance-related acute toxicity deaths is limited, particularly in sub-populations. In response to the overdose crisis, the Public Health Agency of Canada (PHAC), in collaboration with P/T ministries of health and chief coroner and chief medical examiner offices, has undertaken a national chart review study.Objective: This study was conducted to describe and compare the characteristics of substance-related acute toxicity deaths that occurred in Canada between January 1, 2016, and December 31, 2017, including a description of those who have died, the substances involved, and the circumstances surrounding their death. This paper describes the study methodology in detail.Methods: This retrospective population-based cross-sectional study involved the review of coroner and medical examiner files for deaths that met the study case definition. Data were collected on demographic and socioeconomic characteristics, medical and substance use history, proximal circumstances surrounding the death, and toxicology findings using a standardized data collection tool that underwent two pilot studies. Data abstractors underwent training, and adherence to data quality standards was assessed. Data were linked to national datasets to allow for the examination of area-level geographic and socioeconomic characteristics. Descriptive analyses will examine differences across subpopulations and with the general Canadian population, where possible. Latent class, spatiotemporal, qualitative, and premature death analyses are also planned. Where possible,