OBJECTIVE Our study sought to identify sociodemographic, clinical, life perception, and service use characteristics that distinguish new cases of people dependent on substances from the general population; and to determine predictors of substance dependence over a 2-year period. Variables that differentiate people dependent on substances according to sex and age were also assessed. METHODS Among 2434 people who took part in an epidemiologic catchment area health survey at baseline, 2.2% were identified with substance dependence at the second measurement time only. Using a comprehensive framework, various aspects were considered as predictors for multivariate statistics. RESULTS Participants with substance dependence at time 2 only showed worse clinical conditions, life events, life and health perception, and neighbourhood characteristics than other participants, but only 2.5% used health care services. Male sex, younger age, stigmatization, and impulsiveness were predictors of substance dependence. Regarding sex, females with dependence were only more likely to suffer from social phobia than males. In terms of age categories, participants over 50 with substance dependence were more likely to have a lower household income and less social support than younger people. CONCLUSIONS Stigmatization was the strongest predictor of substance dependence. Our study also confirmed that males and younger people were more likely to have substance dependence. Anti-stigmatization, prevention, and outreach programs are needed to overcome the reluctance of this clientele to use health care services. Health professionals should also pay more attention to life and health perception and neighbourhood characteristics of newly identified drug users.