Background: Poor antiretroviral therapy (ART) adherence leads to drug resistance and treatment failures. The options for second and third line ART regimens, particularly for pediatric patients, are very limited in low and middle-income countries. HIV-infected children are mostly passive drug-takers, thus caretakers play a very important role in assuring ART adherence. Pediatric ART adherence is still a challenging problem in Vietnam since non-adherence is the major risk factor for treatment failure. Our study explores and measures caretakers' barriers in order to improve pediatric ART adherence in future. Methods: Exploring caretakers' barriers was conducted through a qualitative study with Focus Group Discussion (FGD) on two topics: 1. Current society - family support and difficulties in taking care children under ART; 2. Stigma experience. Based on the finding from the qualitative study a quantitative study measuring caretakers' barriers was conducted through a designed questionnaire. Study methods strictly followed the consolidated criteria with 32-item checklist for interviews and focus groups. Results: In total eight FGDs with 53 participants were conducted. Common caretakers' barriers to children's ART adherence, were financial burden, lack of ART KP (Knowledge-Practice), stigma, depression, shifting caretaker, drug taste and side effects, lack of family support, fixed health check-up schedule and HIV non-disclosure. In the questionnaire study a total of 209 caretakers participated. The most commonly reported caretakers' barriers were: financial burden (144; 69%), KP burden (143; 68%), depression (85; 41%) and stigma (30; 14.8%). Some caretakers' characteristics that significantly associated with reported barriers (p < 0.05). Rural caretakers reported significantly more financial burden (OR = 2.26) and stigma (OR = 3.53) than urban. Caretakers with under high school level education reported significantly more financial burdens (OR = 2.08) and stigma (OR = 4.15) compared to caretakers with high school education or over. Conclusion: Financial burden, KP burden, depression and stigma were common reported caretakers' barriers to pediatric ART adherence. Family residence, caretaker's education level and job were considered as the key factors determining caretakers' barriers related to financial burden and stigma. These findings may be important for policy makers and researchers in order to develop effective interventions regarding to caretakers' burdens and associated factors. Furthermore, a tool for nurses in monitoring caretakers' barriers to pediatric ART adherence was developed first with FDG, and then interview questionnaire. This tool could be applied and modified easily in any pediatric ART clinic settings in accordance to economic, social and cultural circumstances. [ABSTRACT FROM AUTHOR]