BACKGROUND: In order to clarify priorities and stimulate research in adolescent health in low- and middle-income countries (LMICs), the World Health Organization (WHO) conducted two priority-setting exercises based on the Child Health and Nutrition Research Initiative (CHNRI) methodology related to 1) adolescent sexual and reproductive health and 2) eight areas of adolescent health including communicable diseases prevention and management, injuries and violence, mental health, non-communicable diseases management, nutrition, physical activity, substance use, and health policy. Although the CHNRI methodology has been utilized in over 50 separate research priority setting exercises, none have qualitatively synthesized the ultimate findings across studies. The purpose of this study was to conduct a mixed-method synthesis of two research priority-setting exercises for adolescent health in LMICs based on the CHNRI methodology and to situate the priority questions within the current global health agenda. METHODS: All of the 116 top-ranked questions presented in each exercise were analyzed by two independent reviewers. Word clouds were generated based on keywords from the top-ranked questions. Questions were coded and content analysis was conducted based on type of delivery platform, vulnerable populations, and the Survive, Thrive, and Transform framework from the United Nations Global Strategy for Women's, Children's, and Adolescents' Health, 2016-2030. FINDINGS: Within the 53 top-ranked intervention-related questions that specified a delivery platform, the platforms specified were schools (n = 17), primary care (n = 12), community (n = 11), parenting (n = 6), virtual media (n = 5), and peers (n = 2). Twenty questions specifically focused on vulnerable adolescents, including those living with HIV, tuberculosis, mental illness, or neurodevelopmental disorders; victims of gender-based violence; refugees; young persons who inject drugs; sex workers; slum dwellers; out-of-school youth; and youth in armed conflict. A majority of the top-ranked questions (108/116) aligned with one or a combination of the Survive (n = 39), Thrive (n = 67), and Transform (n = 28) agendas. CONCLUSIONS: This study advances the CHNRI methodology by conducting the first mixed-methods synthesis of multiple research priority-setting exercises by analyzing keywords (using word clouds) and themes (using content analysis).