Abstract Background Understanding factors influencing retention in care (RIC) and viral load improvement (VLI) in people with HIV (PWH) who are out of care and hospitalized will assist in intervention development for this vulnerable population. Methods The study was a post hoc analysis of prospectively collected data. Hospitalized participants were enrolled if they were newly diagnosed with HIV during the hospitalization or out of HIV care. Participants completed surveys at baseline and 6 months postenrollment and laboratory studies of viral load (VL). Outcomes were RIC (2 completed visits, 1 within 30 days of discharge) and VLI (VL <400 or at least a 1-log10 decrease) 6 months after discharge. Univariate and multivariate regression analyses were conducted examining the contributions of predisposing, enabling, and need factors to outcomes. Results The study cohort included 417 participants enrolled between 2010 and 2013. The population was 73% male, 67% non-Hispanic black, 19% Hispanic, and 70% uninsured. Sixty-five percent had a baseline CD4 <200 cells/mm3, 79% had a VL >400 copies/mL or missing, and the population was generally poor with low educational attainment. After discharge from the hospital, 60% did not meet the definition for RIC, and 49% did not have VLI. Modifiable factors associated with the outcomes include drug use (including marijuana alone and other drugs), life instability (eg, housing, employment, and life chaos), and using avoidance coping strategies in coping with HIV. Conclusions Hospitalized out-of-care PWH in the United States are at high risk of poor re-engagement in care after discharge. Interventions for this population should focus on improving socioeconomic stability and coping with HIV and reducing drug use.