Young people including adolescents constitute a significant number of the people living with Human Immune Deficiency Virus/ Acquired Immune Deficiency Syndrome (HIV/AIDS) in the world today. The study sought to establish the antiretroviral treatment adherence determinants among HIV/AIDS infected adolescents in Thika level 5 Hospital. The specific objective of the study was to find out how health literacy influence adherence to antiretroviral treatment among HIV/AIDS infected adolescents, The study was cross sectional and adopted a systematic sampling study design targeting 350 active HIV/AIDS infected adolescent aged between 10-19 years. The study also targeted 25 health care providers (HCPs) delivering care and treatment services to HIV/AIDS infected adolescents in Thika Level 5 hospital. A systematic sampling design was used to get the study respondents, purposive sampling was used to select 25 HCPs . The respondents were selected based on systematic sampling and a sampling interval was calculated. A structured questionnaire and an interview schedule were used as the main tools for data collection. Quantitative data collected was coded and keyed into SPSSv20. The summaries of quantitative findings were presented using tables, figures and discussions. Qualitative data was analyzed using content analysis. Data was grouped into themes and presented in prose form. Frequency counts percentages; Chi-square test and Pearson Product Moment Correlation were used as Descriptive and inferential statistics respectively. The results of the analysis were then presented using tables, column charts and pie charts. 50% of the respondents had difficulty in taking HIV medications, (85.3%) respondents had an abnormal viral load, majority of the respondents viral load was greater than 1000 copies (89.3%).Respondents had normal CD4 counts .The study concludes that health literacy affects adherence to HIV medications among HIV/AIDS infected adolescents in Thika level 5 Hospital. The study recommends that decision-makers come up with relevant social policy to support compliance with HIV medications supplied to adolescent respondents. Majority of the adolescents are most of the time in schools and thus focus to be shifted to school by establishing school health clubs where messages on drugs adherence should be given, the stakeholders in education which includes parents, teachers and pupils and non teaching staff to be empowered on ART adherence so that they can be able to support the adolescents in schools.