Purpose: To compare depression risk among vertically HIV-infected adolescents and matched controls in northern Thailand. Methods: The Thai Children's Depression Inventory (CDI) was administered among vertically HIV-infected adolescents and matched controls in northern Thailand from 2007 to 2008, as part of a comprehensive quantitative survey that also assessed demographics, substance use, and sexual behavior and knowledge. A total CDI score ≥15 was considered a positive screen for possible depression. Results: A total of 54 cases and 165 controls participated; cases had significantly lower mean CDI scores (P =.003) and fewer screened positive for possible depression (P =.046). Cases who screened positive were more likely to have engaged in sexual intercourse (P =.07). Conclusions: Depressive symptoms and depression risk were reduced among vertically HIV-infected adolescents compared to matched controls in northern Thailand. Further investigation into mental health disorders among vertically HIV-infected adolescents in developing settings is needed. © The Author(s) 2011.