The Southeastern United States (US) has a rapidly growing Latino population, yet little is known about HIV-infected Latinos in the region. To help inform future prevention studies, we compared sociodemographic, clinical, and behavioral characteristics between immigrant and US-born HIV-infected Latinos using face-to-face interviews conducted at three clinics in North Carolina. Questions encompassed HIV testing, acculturation, sexual- and substance-related behaviors, and migration history. Behavioral data were compared with 451 black and white clinic patients. Differences were tested using Pearson's and Kruskal-Wallis tests. Participants (n = 127) were primarily male (74%) and immigrants (82%). Most immigrants were Mexican (67%), had low acculturation scores (92%), and were diagnosed a median of 8 years (IQR 0-12) following immigration. Compared with US-born Latinos, immigrants had lower CD4 counts at clinic entry (median 187 vs. 371 cells/mm(3)) and were less likely to have graduated high school (49% vs. 78%) or have insurance (9% vs. 52%; all P <0.05). Most immigrants identified as heterosexual (60%) and reported fewer lifetime partners than US-born Latinos (median 6 vs. 20; P = 0.001). Immigrant men were less likely to report sex with men than US-born men (43% vs. 81%; P = 0.005). Immigrant men also had similar risk behaviors to black men, and US-born Latino men exhibited behaviors that were more similar to white men in our clinic. At the time of survey, >90% of participants were receiving antiretroviral therapy (ART) and most had achieved HIV RNA <50 copies/mL (62% immigrants vs. 76% US-born; P = 0.32). In conclusion, Latino immigrants were more likely to present with advanced disease, identify as heterosexual, and report different risk behaviors than US-born Latinos, yet receipt and response to ART were similar between the two groups. Prevention strategies should prioritize finding innovative methods to reach Latino immigrants for routine early testing regardless of risk stratification and include programs targeted toward the different needs of immigrant and US-born Latinos.