Drinking, smoking, and health risk behaviors are significant problems for Thai adolescents. However, little is known about the association and magnitude among alcohol, tobacco, or co-using and health risk behaviors. Data of the National School Survey of 2007 were analyzed. The sample consisted of 50,033 high school and vocational college students. The interaction between gender and drinking-smoking status was significant for all health risk behaviors except for having sex and unprotected sex. Alcohol and tobacco had a stronger association with illegal substance use in boys than in girls. In contrast, their use had a stronger association with fighting, depression, and suicidal thoughts in girls than in boys. The intervention program for Thai youths in school should take into account the strong relationship between alcohol-tobacco consumption and these health risk behaviors. (Contains 3 tables.)