Introduction: Many drugs, including cannabis and alcohol, cause impairment and contribute to motor vehicle collisions (MVCs). Policy makers require knowledge of the prevalence of drug use in crash-involved drivers, and types of drugs used in order to develop effective prevention programs. This issue is particularly relevant with the recent legalization of cannabis. We aim to study the prevalence of alcohol, cannabis, sedating medications, and other drugs in injured drivers from 4 Canadian Provinces. Methods: This prospective cohort study obtained excess clinical blood samples from consecutive injured drivers who attended a participating Canadian trauma centre following a MVC. Blood samples were analyzed using a broad spectrum toxicology screen capable of detecting cannabinoids, cocaine, amphetamines (including their major analogues), and opioids as well as psychotropic pharmaceuticals (including antihistamines, benzodiazepines, other hypnotics, and sedating antidepressants). Alcohol and cannabinoids were quantified. Health records were reviewed to extract demographic, medical, and MVC information using a standardized data collection tool. Results: This study has been collecting data in 4 trauma centres in British Columbia (BC) since 2011 and was launched in 2 trauma centres in Alberta (AB), 1 in Saskatchewan (SK), and 2 in Ontario (ON) in 2018. In preliminary results from BC (n = 2412), 8% of injured drivers tested positive for THC and 13% for alcohol. Preliminary results from other provinces (n = 301) suggest a regional variation in prevalence of drivers testing positive for THC (10% - 27%), alcohol (17% - 29%), and other drugs. By May 2018, an estimated 4500 cases from BC, 600 from AB, 150 from SK, and 650 from ON will have been analyzed. We will report the prevalence of positive tests for alcohol, THC, other recreational drugs, and sedating medications, pre and post cannabis legalization. The number of cases with alcohol and/or THC levels above Canadian per se limits will also be reported. Results will be reported according to province, driver sex, age, single vs. multi vehicle crashes, and requirement for hospital admission. Conclusion: This will be among the largest international datasets on drug use by injured drivers. Our findings will provide patterns of drug and alcohol impairment in 4 Canadian provinces pre and post cannabis legalization. The significance of these findings and implication for impaired driving policy and prevention programs in Canada will be discussed.