As drugs remain ubiquitous and their use increasingly viewed as socially normative, vulnerable population groups such as adolescents face continued and growing risk. A better understanding of the factors that discourage individuals from initiating drug use, particularly in enabling scenarios, is therefore needed. This study aims to identify individual, interpersonal and school-contextual factors associated with resistance to using drugs in the presence of a drug use opportunity among adolescents in Bogotá, Colombia.Data are analyzed from 724 school-attending adolescents (15.1 years, SD=1.3) who have had an opportunity to use drugs. Schools were selected in a multistage probability cluster sample. Random intercept multilevel logistic regression models were implemented to estimate the effect of individual, interpersonal and school-contextual level variables on the likelihood of resisting using drugs.Drug use resistance was observed in less than half (41.4%) of those students who experienced an opportunity to use drugs. Drug use resistance was strongly associated with having experienced a passive drug use opportunity (AOR=3.1, 95% CI=2.0, 4.9), the number of drugs offered (AOR=0.7, 95% CI=0.6, 0.8) and family factors such as not having a drug-using first-degree relative (AOR=2.3, 95% CI=1.2, 4.3) and a high degree of parental supervision (AOR=1.9, 95% CI=1.0, 3.2).A large proportion of students who experienced a drug-use opportunity did not initiate drug use despite living in a context of high drug availability and social disorganization. The findings highlight the need for effective family-based drug use prevention interventions within the Colombian context.