Individuals with HIV experience fluctuating levels of distress throughout the course of HIV infection. This study was conducted to examine the associations of depressive symptomatology with HIV disease in a cohort of individuals who are engaged in routine medical care. This cross-sectional study examined the prevalence of depressive symptoms that were measured as part of a standard of care behavioral assessment among individuals at an urban HIV clinic in the Midwest. Demographic characteristics, depressive symptoms, and behavioral risk factors were collected. A total of 514 individuals participated in the study, the majority of whom was male and African American. One quarter of the sample endorsed symptoms of other depressive disorder, while 18% (n=91) endorsed symptoms of major depressive disorder as measured by the Patient Health Questionnaire-9 (PHQ-9). Among those on highly active antiretroviral therapy (HAART), individuals who were unemployed (adjusted odds ratio [AOR]=2.47, 95% confidence interval [CI]=1.54, 3.97), had a minor dependent (AOR-2.17, 95% CI=1.25, 3.77), or between the ages of 18 and 34 years (AOR=1.37, CI=1.03, 1.94) and detectable HIV viral load (AOR=2.52, 95% CI=1.22, 5.23) were more likely to report depressive disorder symptoms when controlling for age, gender, race, and education. Nearly 15% of the sample endorsed having suicidal thoughts at least once in the past two weeks. Regardless of HAART prescription, individuals who were unemployed had a higher likelihood of expressing suicidal ideation (AOR=3.43, 95% CI=1.66, 7.06). Given the association between depressive symptomatology and poor rates of HIV viral suppression, screening and appropriate interventions for depressive symptoms are warranted in the HIV outpatient setting to improve outcomes. © 2009, Mary Ann Liebert, Inc.