The Health Behaviour in School-aged Children (HBSC) study is a large school-based survey conducted every four years in collaboration with the WHO Regional Office for Europe. The data collected from this study are utilized at national, regional, and international levels to gain a deeper understanding of adolescent health and well-being, identify social determinants of health, and guide policy and interventions to enhance the lives of young people. The 2021/2022 HBSC survey results are presented in a series of volumes focusing on specific health topics. Volume 3 of this series examines adolescent substance use, drawing on data from adolescents aged 11, 13, and 15 years across 44 countries and regions in Europe, central Asia, and Canada. This report analyzes the prevalence of substance use among adolescents, including cigarette smoking, electronic cigarette use, alcohol consumption, drunkenness, and cannabis use. The report also explores the influence of gender, age, and social inequality on substance use patterns, as well as changes in substance use trends over time. The findings from the 2021/2022 HBSC survey serve as a crucial reference point for ongoing research, interventions, and policy-making efforts.