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Background Substance abuse among adolescents is a major public health and social problem. However, studies rarely investigate the relationships between substance abuse, educational achievement and sport factors. Substance abuse is an even more significant problem in societies that have experienced trauma, such as Bosnia and Herzegovina, which have had recent wars. The aims of this study were to investigate substance abuse among adolescents in Bosnia and Herzegovina and to study the potential gender-specific relationships between a) sport factors (physical activity/exercise/athletic participation) and substance abuse and b) scholastic achievement and substance abuse. Methods Our sample consisted of 1,032 adolescents who were 17 to 18 years old (435 boys and 597 girls) and who were in the final grade of high school. These subjects were randomly selected from the territory of Herzegovina-Neretva Canton of Bosnia and Herzegovina. Retrospective testing was performed using an extensive self-administered questionnaire. The questionnaire included questions involving topics such as sociodemographic variables, scholastic variables, sport factors, and substance abuse data (smoking habits, drugs consumption and alcohol consumption using the AUDIT questionnaire). Descriptive statistics, frequencies, analyses of the differences and correlational analyses were performed. Results Our results found that greater than one-third of the boys and one-fourth of the girls were daily smokers, and almost half of the boys and one-fifth of the girls practiced harmful drinking; other drugs (i.e. heroin, cocaine, amphetamines, etc.) were rarely consumed. Boys dominated in sport factors, whereas girls were more successful in scholastic achievement. Approximately 23% of the boys and 6% of the girls reported that they practiced harmful drinking and smoked simultaneously. Educational failure, which was defined as having one or more negative grades at the end of the last two school years, was identified in 20% of the boys and 9% of the girls. In both genders, substance abuse was negatively correlated with educational achievement, and half of those students who failed educationally reported daily smoking. Among the girls who experienced education failure, 33% were smokers, and 22% practiced harmful drinking. Sport factors were weakly correlated with substance abuse in boys; thus, we could not support the hypothesis that sports are a protective factor against substance abuse among male adolescents. In girls, participation in team sports was related with a higher incidence of smoking, but there was no evidence of sport factors having an influence on the consumption of alcohol. Conclusion In this study, the incidence of smoking and the consumption of alcohol were alarmingly high. These findings demonstrate the need for intervention programs to address these issues. These problems are particularly important, considering that substance abuse has a negative impact on educational achievement among boys and girls, and sport factors have not been found to be protective factors against substance abuse.