Purpose: To examine the association between alcohol use and psychological distress among adolescents in a range of developing countries. Methods: Secondary data analysis of the Global School-Based Student Health Survey was conducted using nationally representative data from 12 developing countries: Botswana, Grenada, Indonesia, Kenya, Myanmar, the Philippines, Saint Lucia, Saint Vincent and the Grenadines, the Seychelles, Thailand, Trinidad and Tobago, and Uganda. The surveys were conducted between 2003 and 2008 and involved 32,001 adolescents primarily aged 13e15 years. We used multivariate logistic regression analysis to determine the association between alcohol use and psychological distress. Results: The prevalence of past 30-day alcohol use and lifetime drunkenness varied widely across countries, as did the occurrence of psychological distress (anxiety-induced sleeplessness and/or depression). The risk of psychological distress was significantly higher among adolescents when using alcohol in all countries except Myanmar. In nine of the 12 countries, past 30-day alcohol use was associated with psychological distress, while students who had been drunk at least once in their lifetime had an increased risk of experiencing psychological distress in 11 of the study countries. Conclusions: The high prevalence of alcohol use among adolescents and the strength of the association with psychological distress present a major public health challenge in developing countries. The urgent need to reduce adolescent alcohol use necessitates the implementation of context- and culture-specific strategies that reduce the physical availability of alcohol.