Background: Studies from sub-Saharan Africa (SSA) document how barriers to ART adherence present additional complications among adolescents and young adults living with HIV. We qualitatively explored barriers to ART adherence in Uganda among individuals age 14-24 to understand the unique challenges faced by this age group. Methods: We conducted focus group (FG) discussions with Community Advisory Board members (n = 1), health care providers (n = 2), and male and female groups of adolescents age 14-17 (n = 2) and youth age 18-24 (n = 2) in Kampala, Uganda. FGs were transcribed verbatim and translated from Luganda into English. Two investigators independently reviewed all transcripts, developed a detailed codebook, achieved a pooled Cohen's Kappa of 0.79 and 0.80, and used a directed content analysis to identify key themes. Results: Four barriers to ART adherence emerged: 1) poverty limited adolescents' ability to buy food and undercut efforts to become economically independent in their transition from adolescence to adulthood; 2) school attendance limited their privacy, further disrupting ART adherence; 3) family support was unreliable, and youth often struggled with a constant change in guardianship because they had lost their biological parents to HIV. In contrast peer influence, especially among HIV-positive youth, was strong and created an important network to support ART adherence; 4) the burden of taking multiple medications daily frustrated youth, often leading to so-called 'drug holidays.' Adolescent and youth-specific issues around disclosure emerged across three of the four barriers. Conclusions: To be effective, programs and policies to improve ART adherence among youth in Uganda must address the special challenges that adolescents and young adults confront in achieving optimal adherence. For example, training on budgeting and savings practices could help promote their transition to financial independence. School staff could develop strategies to help students take their medications consistently and confidentially. While challenging to extend the range of services provided by HIV clinics, successful efforts will require engaging the family, peers, and larger community of health and educational providers to support adolescents and young adults living with HIV to live longer and healthier lives. Trial registration: ClinicalTrials.gov Identifier: NCT02514356. Registered August 3, 2015.