Abstract Background Substance use among adolescents with health conditions and disabilities is an important issue in public health and pediatrics that warrants further study. Existing research typically investigates one type of health condition and/or disability, which limits understanding of how substance use is similar or different across various sub-groups. By including multiple sub-groups and adolescents who report no conditions, the results of our research could be used to inform targeted interventions and supports. Objectives The purpose of this study was to investigate substance use among adolescents across multiple categories of health conditions and/or disabilities using data from the 2013 British Columbia Adolescent Health Survey (BCAHS) (see Table 1). The research objectives were: 1) to determine the number of (categories of) substances used by survey respondents; 2) to investigate the occurrence (frequency) of respondents’ substance use; 3) to explore the consequences of their substance use; and 4) to ascertain the reasons for their substance use. Design/Methods This was a secondary analysis of data from the 2013 British Columbia Adolescent Health Survey, which is quinquennially administered by the McCreary Centre Society. The BCAHS is a large-scale survey designed to capture information about adolescents’ physical and emotional health, and about factors that can influence health during adolescence and in later life. The study population consisted of a total provincial weighted N = 251,641 of adolescents from 56 (of 59) school districts who attended Grade 7 to Grade 12 in the 2012/2013 school year. We performed a series of descriptive statistical analyses on the person-level database, including frequencies and cross-tabulations. Statistical analyses were conducted using the Complex Samples module of IBM SPSS Statistics, Version 24 (IBM Corp, 2016), which facilitates the computation of statistics and standard errors from complex sample designs while adjusting for the complex cluster-stratified sampling method and weighted data by integrating sample designs into survey analysis. Results The results indicated great diversity, both within and between categories of health conditions and/or disabilities. In particular, we found that youth in three categories: those with mental or emotional needs, those with behavioural needs, and those with two or more conditions were i) using the greatest number of (categories of) substances, ii) using substances most frequently, and iii) were experiencing the most severe consequences as a result of substance use. Conclusion Clearly there is a need for greater access to mental health supports, including assessment and treatment, for adolescents. Further, given that youth with two or more conditions were also more likely to engage in substance use, there is a need for complex care programs to support this sub-group. Lastly, as adolescents are approaching the transition from pediatrics to adult healthcare services, substance use programming that bridges these developmental stages is needed.