BACKGROUND: Prior authorizations (PAs) may improve appropriate use of prescription medications. Despite potential savings for health insurance plans, the PA process is time consuming for the ordering provider, pharmacy, and patient. The UC Davis Health System (UCDHS) has created a centralized pharmacy-run clinic PA process. OBJECTIVE: To compare the mean PA processing time between the new centralized clinic and usual care and provide secondary endpoints for PA approval rates, time to prescription fill, time to prescription pick-up, total staff time, and estimated labor costs. METHODS: This is a prospective observational study comparing sequential PA requests at the UCDHS centralized clinic (intervention) and other UCDHS clinics (usual care) between January 1, 2014, and December 31, 2014. The Cochran-Mantel-Haenszel test was used to compare dichotomous outcomes (approval/denial rates) between the 2 groups, controlling for insurance type. A generalized linear model was applied for comparing the continuous outcomes (PA process time, time to first fill, time to pick-up, and cost) with insurance type as covariate. RESULTS: For the intervention group, 47 PAs were evaluated, and 77 PAs were evaluated in the usual care group. The average PA process time was 0.53 days for the intervention group versus 7.02 days for usual care (P < 0.001), and the PA approval rate was 93% for the intervention group versus 68% for usual care (P < 0.002). The mean time to fill was 2.49 days and 5.52 days for the intervention and usual care clinics, respectively (P = 0.02). The pick-up percentage was 75% versus 52% for intervention and usual care, respectively (P < 0.001). The intervention clinic spent a significantly lower mean time processing PAs (15 minutes vs. 64 minutes) compared with the usual care clinics (P < 0.001). It is estimated that the mean total labor cost per PA at the intervention clinic was $11.50 compared with $37.50 for the usual care clinics (P < 0.001). CONCLUSIONS: Pharmacy-led interventions in PA processing resulted in a statistically significant benefit in improving time to PA approval, time to first fill, and time to pick-up. DISCLOSURES: No outside funding supported this study. The authors report no conflicting interests. Melnikow and Cutler contributed the study concept and design, with assistance from the other authors. Lester, Barca, and She collected the data, and Xin performed all statistical analysis. Cutler was the major contributor to manuscript preparation, with assistance from the other authors.