Background: Social capital has lately received much attention in public health research. However, few studies have examined the influence of social capital on alcohol consumption, smoking and drug use which have strong influence on public health. The present cross-sectional study investigated whether two measures of social capital were related to substance use in a large population of Swedish adolescents. Methods: A total of 7757 13-18 year old students (participation rate: 78.2%) anonymously completed the Survey of Adolescent Life in Vestmanland 2008 which included questions on sociodemographic background, neighbourhood social capital, general social trust, alcohol consumption, smoking, and illicit drug use. Results: Individuals within the group with low neighbourhood social capital had an approximately 60% increased odds of high alcohol consumption, more than three times increased odds of smoking and more than double the odds of having used illicit drugs compared with individuals with high neighbourhood social capital. Individuals within the group with low general social trust had approximately 50% increased odds of high alcohol consumption and double the odds of smoking and having used illicit drugs compared with individuals with high general social trust. However, social capital at the contextual level showed very weak effects on alcohol consumption, smoking, and illicit drug use. Conclusions: Social capital may be an important factor in the future development of prevention programs concerning adolescent substance use. However, further replications of the results as well as identifications of direction of causality are needed.