Objective:To evaluate alcohol/tobacco and/or illicit drug misuse in Chronic Diseases (CDs).Methods:A cross-sectional study with 220 CDs adolescents and 110 healthy controls including: demographic/anthropometric data; puberty markers; modified questionnaire evaluating sexual function, alcohol/smoking/illicit drug misuse and bullying; and the physician-conducted CRAFFT (car/relax/alone/forget/friends/trouble) screen tool for substance abuse/dependence high risk.Results:The frequencies of alcohol/tobacco and/or illicit drug use were similar in both groups (30% vs. 34%, p=0.529), likewise the frequencies of bullying (42% vs. 41%, p=0.905). Further analysis solely in CDs patients that used alcohol/tobacco/illicit drug versus those that did not use showed that the median current age [15 (11–18) vs. 14 (10–18) years, p <0.0001] and education years [9 (5–14) vs. 8 (3–12) years, p <0.0001] were significant higher in substance use group. The frequencies of Tanner 5 (p <0.0001), menarche (p <0.0001) and spermarche (p=0.001) were also significantly higher in patients with CDs that used alcohol/tobacco/illicit, likewise sexual activity (23% vs. 3%, p <0.0001). A trend of a low frequency of drug therapy was observed in patients that used substances (70% vs. 82%, p=0.051). A positive correlation was observed between CRAFFT score and current age in CD patients (p=0.005, r=+0.189) and controls (p=0.018, r=+0.226).Conclusions:A later age was evidenced in CDs patients that reported licit/ilicit drug misuse. In CDs adolescent, substance use was more likely to have sexual intercourse. Our study reinforces that these patients should be systematically screened by pediatricians for drug related health behavioral patterns.