Transitioning to adult care for HIV-infected adolescents is a critical process in determining long-term health outcomes. Poor transitioning to adult care can lead to several adverse HIV-related outcomes for adolescents living with HIV, including disruption of care, non-adherence to ART and virological failure. In this qualitative study, we explore the barriers to and facilitators of the transition to adult care among HIV-infected youth from the perspectives of health care workers and allied staff. We enrolled 24 health care workers and allied staff from two infectious diseases clinics in the Western Cape of South Africa. Participants took part in a once-off, semi-structured interview that was conducted face-to-face at the respective clinics. Interviews were audio-recorded and transcribed verbatim for thematic analysis using ATLAS.ti. Two superordinate themes and seven subthemes emerged from the data. We found that barriers to the transition process were related to a lack of preparedness and readiness to transition at both an institutional level and at the level of the caregiver and adolescent. At the institutional level, a lack of a transition policy and limited time and resources available for the transition process were salient barriers. At the caregiver-adolescent level, adolescents’ desire for normality and caregivers’ reluctance to devolve responsibility of care to their children were important barriers to the transition process. Facilitators prepare adolescents and caregivers for transition from an early age. Our findings highlight the importance of considering both adolescent, caregiver and institutional factors when preparing for the transition process. Our findings also show that pressure on the health care system precludes the time required for this process. However, counselling for transition from an early age might be an important way to negate these issues.