© 2018 The Author(s). Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. Regional variability in human immunodeficiency virus (HIV) care engagement remains underexplored. Multiple logistic models compared HIV outcomes for participants from 5 Southern (n = 557) and 6 non-Southern (n = 670) sites. Southern participants were less likely to experience viral suppression (adjusted odds ratio [aOR], 0.52; 95% confidence interval [CI],.37-.72) and had a higher likelihood of a CD4+ count <200 cells/μL (aOR, 1.53; 95% CI, 1.17-2.00). HIV intervention and social safety net programs should be expanded. Clinical Trials Registration NCT01612169.