BACKGROUND: Treatment-related reductions in morbidity and mortality among human immunodeficiency virus (HIV)-positive patients have been attenuated by cigarette smoking, which increases risk of cardiovascular, respiratory, and neoplastic diseases. This study investigated factors associated with smoking status among HIV-positive patients. METHODS: This cross-sectional study included 2,464 HIV-positive patients attending the HIV Clinic at the University of Alabama at Birmingham between April 2008 and December 2013. Smoking status (current, former, never), psychosocial factors, and clinical characteristics were assessed. Multinomial logistic regression was used to obtain unadjusted and adjusted odds ratios (OR) and 95% confidence intervals (CI) for the association of the various factors with smoking status. RESULTS: Among HIV-positive patients (mean age 45 years, 75% male, 55% African-American), the majority reported a history of smoking (39% current and 22% former smokers). In adjusted models, patient characteristics associated with increased odds of current smoking were male gender (OR for heterosexual men, 1.8 [95% CI: 1.3-2.6]; for men who have sex with men, 1.5 [1.1-1.9]), history of respiratory diseases (1.5 [1.2-1.9]), unsuppressed HIV viral load (>50 copies/mL) (1.5 [1.1-1.9]), depression (1.6 [1.3-2.0]), anxiety (1.6 [1.2-2.1]), and prior and current substance abuse (4.7 [3.6-6.1] and 8.3 [5.3-13.3] respectively). Male gender, anxiety, and substance abuse were also associated with being a former smoker. CONCLUSIONS: Smoking was common among HIV-positive patients, with several psychosocial factors associated with current and former smoking. This suggests smoking cessation programs in HIV clinic settings may achieve greater impact by integrating interventions that also address illicit substance abuse and mental health.