Objectives: Addressing structural barriers to care for people living with human immunodeficiency virus (HIV) in the southern United States is critical to increase rates of viral suppression and to reduce existing HIV disparities. This qualitative study aimed to describe transportation-related barriers experienced by people living with HIV in South Carolina, understand perceived effects of transportation vulnerability on HIV care, and explore strategies used by individuals to overcome transportation-related challenges., Methods: We conducted semistructured interviews with 20 people living with HIV from South Carolina who were either reengaging in HIV care after a prolonged absence (>9 months) or in care but with a detectable viral load (ie, >200 copies/mL). All people living with HIV reported transportation vulnerability. A deductive/inductive approach was used to identify transportation-related barriers perceived to negatively affect HIV care. We also identified strategies and resources described by people living with HIV as helpful in addressing transportation challenges., Results: Participants described a range of transportation-related barriers to HIV care, including lack of access to reliable, safe, and affordable transportation, as well as stigma due to HIV and socioeconomic statuses. These barriers were reported to negatively affect engagement in care and worsen both physical and mental health. Participants indicated flexible clinic policies and instrumental support from family and friends were useful in overcoming barriers., Conclusions: This study offers insight for the development of transportation interventions to improve equitable access to HIV care for people living with HIV in South Carolina. It also calls attention to the ways in which transportation vulnerability, HIV-related stigma, and disability status intersect to create unique challenges for some people living with HIV.