Objectives: The objective was to assess the acceptance of an emergency department (ED) human immunodeficiency virus (HIV) screening program based on the Centers for Disease Control and Prevention (CDC) recommendations for routine HIV screening in health care settings.Methods: Rapid HIV screening was offered on an opt-out basis to patients aged 13 to 64 years presenting to the ED by trained HIV counselors. Patients were excluded if they had a history of HIV, were physically or mentally incapacitated, did not understand their right to opt-out, or did not speak English or Spanish. Statistical analyses, including logistic regression, were performed to assess the associations between the demographics of patients offered testing and their test acceptance or refusal.Results: From March 2008 to January 2009, a total of 5,080 (91%) of the 5,585 patients offered the HIV test accepted, and 506 (9%) refused. White and married patients were less likely to accept testing than those who were African American and unmarried (p < 0.001). Adult patients were almost twice as likely to accept testing as pediatric patients (odds ratio [OR] = 1.95; 95% confidence interval [CI] = 1.50 to 2.53). As age increased among pediatric patients, testing refusal decreased (OR = 0.71; 95% CI = 0.59 to 0.85), and as age increased among adult patients, testing refusal increased (OR = 1.17; 95% CI = 1.12 to 1.22). Two percent of persons accepting the test were considered high risk. Males were more likely to report high-risk behavior than females (OR = 1.83; 95% CI = 1.23 to 2.72).