Introduction: The goals of this study were to analyze possible trends of fatal and serious injuries related to vulnerable road users in Canada (pedestrians, cyclists and motorcyclists) from 1990 to 2012 and the role of alcohol and drugs in these cases. Drugs have rarely been documented with respect to vulnerable road users., Method: The Traffic Injury Research Foundation's National Fatality and Serious Injury Databases and the Public Health Agency of Canada's Canadian Hospitals Injury Reporting and Prevention Program databases were used. Numbers and rates of fatalities and serious injuries among vulnerable road users were analyzed and regression models were used to assess changes over time., Results: The analyses show that while the absolute number of fatalities and the rate per 100,000 population among vulnerable road users may be decreasing, no such trends are apparent when looking at the proportions of these road user fatalities out of all motor-vehicle fatalities. The trend for the proportion of motorcyclist fatalities is significantly increasing (coef.=0.16, p<0.001). The elderly (76years or older) are overrepresented among pedestrian fatalities, and serious injuries (they represent 18.5% of all pedestrian fatalities but only 5.8% of the population), while those 15years or younger are overrepresented among cyclists (they represent 23.3% of cyclist fatalities but 19.5% of the population), and those 16 to 25years old are overrepresented among motorcyclists (27.2% of motorcyclists fatalities and 13.6% of population). Alcohol and drug use among fatally injured vulnerable road users were significant problems, especially among pedestrians. Among fatally injured pedestrians tested for alcohol and drugs, 39.7% and 43.4% tested positive, respectively., Conclusions: With the promotion of walking and cycling as forms of exercise and the popularity of motorcycling, the safety of vulnerable road users is an important issue. The results corroborate previous research and extend our understanding about the influence of alcohol and drugs in vulnerable road user injuries., Practical Applications: These findings can help better inform prevention and mitigation initiatives for vulnerable road users., (Copyright © 2016 Elsevier Ltd and National Safety Council. All rights reserved.)