BACKGROUND: Individuals infected with human immunodeficiency virus (HIV) are at increased risk for cardiovascular disease (CVD) events compared with uninfected persons. However, little is known about HIV provider practices regarding aspirin (ASA) for primary prevention of CVD. METHODS: A cross-sectional study was conducted among patients attending the University of Alabama at Birmingham 1917 HIV Clinic during 2010 to determine the proportion receiving ASA for primary prevention of CVD and identify factors associated with ASA prescription. Ten-year risk for CVD events was calculated for men aged 45-79 and women aged 55-79. The 2009 US Preventive Services Task Force (USPSTF) guidelines were used to determine those qualifying for primary CVD prevention. RESULTS: Among 397 patients who qualified to receive ASA (mean age, 52.2 years, 94% male, 36% African American), only 66 (17%) were prescribed ASA. In multivariable logistic regression analysis, diabetes mellitus (odds ratio [OR], 2.60; 95% confidence interval [CI], 1.28-5.27), hyperlipidemia (OR, 3.42; 95% CI, 1.55-7.56), and current smoking (OR, 1.87; 95% CI, 1.03-3.41) were significantly associated with ASA prescription. Odds of ASA prescription more than doubled for each additional CVD-related comorbidity present among hypertension, diabetes, hyperlipidemia, and smoking (OR, 2.13, 95% CI, 1.51-2.99). CONCLUSIONS: In this HIV-infected cohort, fewer than 1 in 5 patients in need received ASA for primary CVD prevention. Escalating likelihood of ASA prescription with increasing CVD-related comorbidity count suggests that providers may be influenced more by co-occurrence of these diagnoses than by USPSTF guidelines. In the absence of HIV-specific guidelines, interventions to improve HIV provider awareness of and adherence to existing general population guidelines on CVD risk reduction are needed.