Background: Introduction of highly active antiretroviral therapy (HAART) has resulted in a significant decrease of oral manifestations (OMs). The profile and risk factors for OM in those individuals initiating HAART remain understudied in the Southeast of the United States, region of increasing HIV prevalence. Objective: To determine clinical, socio-demographic, and laboratory characteristics associated with the presence of OM among patients initiating HAART. Methods: Retrospective review of electronically captured data from patients initiating HAART at a Southeastern US clinic. Prevalence was determined, and risk factors for overall OM, oropharyngeal candidiasis (OPC), and all other OM were evaluated using logistic regression. Results: In our sample (n = 744), majority of individuals were males (75 percent), African-American (50 percent), mean age of 39 years, 42 percent of which reported sex with men (MSM). Two hundred sixty-six had some type of OM. Compared with those without any OM, patients with OM had a lower mean baseline CD4+ T cells count (CD4 count) (331 ± 260 versus 179 ± 244 CD4 cells/mm 3) and higher mean baseline HIV-1 RNA viral load (4.0 ± 1.34 log 10 versus 4.6 ± 1.30 log 10) (P < 0.01). In the logistic regression models seeking to determine factors associated with an increased risk of OM and OPC, the only characteristic associated with the outcome was baseline CD4 value. Being male, African-American, and heterosexual showed a protective role for OM other than OPC. Conclusion: OM continues to be common despite HAART. General OM and OPC were closely associated with a low baseline CD4 count. Knowledge of risk factors for OM can potentially help clinicians target oral evaluation of HIV-positive individuals. © 2011 American Association of Public Health Dentistry.