Aim: The article describes similarities and differences regarding various risk factors between girls and boys with substance abuse problems who begin outpatient treatment at the Maria clinics in Sweden. Potential hypotheses and some implications are also discussed. Methods: This cross-sectional study was based on interview data from 2169 adolescents obtained over three years from outpatient clinics in 11 Swedish cities. Results: Girls appear to consistently have more difficult family and childhood environments than boys, and are more likely to have problems related to school, more serious substance abuse problems, and more severe mental health problems. Criminal activity is significantly higher among boys. Conclusions: The study shows that girls entering treatment generally have significantly more risk factors than boys and thus more extensive problems in several aspects of life, which in turn increases the risk of developing serious drug and alcohol problems in adulthood. The study supports the gender-paradoxical relationship in which a smaller proportion of girls than boys enter treatment for substance abuse, even though girls tend to have more problematic life situations.