OBJECTIVES: To examine whether the average direct medical costs paid for adult vaccination differed by the vaccination setting. METHODS: An observational retrospective study using 2010 MarketScan® Commercial Claims and Encounters, and Medicare Supplemental databases.  Adults receiving ZOSTAVAX® (herpes zoster or shingles vaccine), PNEUMOVAX® 23 (pneumococcal vaccine), or influenza vaccines were identified using CPT and NDC codes from medical and pharmacy claims files, respectively.  The vaccination costs included the health plan and enrollee paid amounts for the product, vaccine administration, and where applicable, the visit.  The mean (SD) vaccination costs paid per vaccine administration were examined by vaccine and type of setting including physician offices, pharmacies, and other medical settings (e.g., inpatient/outpatient hospitals, emergency rooms) RESULTS: Of those receiving ZOSTAVAX®, PNEUMOVAX® 23 and influenza vaccines, 25%, 1%, and 7%, respectively, received it at a pharmacy.  Compared to other US regions, pharmacy-based vaccination for these 3 vaccines was generally higher in the western and southern regions.  Overall, the mean (SD) paid amounts per enrollee per vaccine administration at the physician offices, pharmacies, and other medical settings were as follows: ZOSTAVAX® $208.7 (42.1), $168.5 (15.7), and $209.5 (50.8), respectively (p<0.05); PNEUMOVAX® 23 $65.6 (27.5), $55.0 (9.7), and $72.1 (50.0), respectively (p<0.05); and influenza $29.3 (15.3), $21.6 (6.6), and $24.2 (13.1), respectively (p<0.05).  The mean paid amounts also differed by geographic regions and type of health plan, with costs usually lower for the vaccinations given at the pharmacies.  CONCLUSIONS:  The average direct costs per adult vaccination were lower in pharmacies, compared to physician offices and other medical settings by 16-26% and 11-20 %, respectively.  These results were mostly consistent across geographic regions and types of health plans.  These data may help payer and policymaker understand economic value of adult vaccination in different settings, especially in pharmacies.