The research on substance (alcohol, tobacco and drug) abuse and on self-perception was done by comparing a test group of physically disabled adolescents and a test group of non-disabled adolescents. The respondents of the experimental group were students of the only special high school for physically handicapped persons in Croatia, Zagreb. The respondents of the control group were the students of two regular high schools in the capital of Croatia. The instrument used in this research was a self-reported, anonymous questionnaire. The respondents completed the questionnaire in the classroom. The data analysis regarding alcohol abuse indicated that physically disabled adolescents drink more often and out of quite different motives than their non-disabled peers. Regarding the prevalence, frequency, quantity and motives for smoking, no statistically significant difference has been found between the tested groups. On the contrary, significant differences between handicapped and non-disabled adolescents were evident regarding drug abuse. Only one physically disabled examinee used a drug – marijuana, only a few times a year. On the other hand, almost one quarter of the non-disabled adolescents use at least one, five at the most, type of drug sometimes or often. The results on the self-perception scale show that adolescent with physical disabilities have a much more negative attitude toward themselves than non-disabled controls. Their self-esteem and self-confidence are seriously diminished. Described findings could have a mighty impact on ways of preventing substance abuse, and on ways of increasing self-esteem among disabled and non-disabled adolescents.