Although prior authorization (PA) for prescription medications is widely employed for cost-containment for third-party insurers, it is a frustrating aspect of outpatient clinical care that imposes uncompensated costs to medical providers. To characterize these costs, we monitored the PA-associated administrative and operational process at the University of Alabama at Birmingham 1917 HIV Clinic over a 2-year period. A total of 288 PAs were processed with a mean (± standard deviation [SD]) of days 3.1±5.8 delay in the patient's access to medication. A mean (±SD) of 26.8±18.4 min was spent by the nurse practitioner and 6.5±2.9 min was spent by a clerk per PA. Nearly three-quarters (73%) of PAs were approved, 18% were denied, and 10% were voided. The mean (±SD) pages of paperwork was 5.8±6.5. The overall cost was $41.60 per PA. Although evidence supports that PA reduces third-party expenditures, it significantly delays medication accessibility for patients and imposes high costs that negatively impact operating margins for health care providers. © 2010 by the Infectious Diseases Society of America.