OBJECTIVES: The Post-Licensure Rapid Immunization Safety Monitoring (PRISM) program was created in response to the need of the U.S. Food and Drug Administration (FDA) to monitor the safety of H1N1influenza vaccine.  Later PRISM was incorporated into the FDA’s Mini-Sentinel Initiative to evaluate the safety of other vaccines. We describe the distributed data structure used in this system. METHODS: PRISM uses a distributed data method whereby claims data processed through 3 health insurance companies, “Data Partners,” are organized into a standardized common data model (CDM).  Data in this standard format are refreshed on a quarterly basis and stored by the Data Partners.  Mini-Sentinel programs are run on these data to extract aggregate data for analysis.  The data in the CDM are augmented by linking to eight state and city Immunization Information Systems (IIS) to obtain additional vaccine exposure data.  RESULTS: The CDM includes 110 million lives, 2.6 billion dispensing, and 3.1 billion healthcare encounters from 2004-2012 from the three Data Partners, representing three major health insurance companies. The vaccine data from the state IIS improve the completeness of vaccine information for individuals.  In 2012, unrestricted (including states even if they did not contribute data) analysis showed that IIS contributed an additional 5-9% of vaccine administration data. In the chart validation assessing the risk of intussusception following rotavirus vaccination, it was identified that 46% (124/267) of cases identified by the electronic algorithm were true intussusception cases.   Reports on one vaccine safety assessment has been completed. CONCLUSIONS: Vaccines are an essential component to maintain public health. The benefits of the PRISM system include the large pooled population, enhanced ability to capture data from alternative sources, and ability to evaluate the potential risks of rare adverse events; the distributed data model ensures patient confidentiality.  Validation by chart review adds precision to the evaluations.