Interoperable support of electronic health records and clinical decision support technology are central to the vision of sustainable information infrastructure. Efforts to implement interoperable clinical guidelines for immunization practice have been sparse. We used the SAGE knowledge workbench to develop a knowledge base to provide immunization decision support in primary care. We translated the written clinical guideline into a structured decision logic format. The semantic content to completely capture CDC clinical decision logic required 197 separate concepts but was completely captured with SNOMED CT and LOINC. Although 88% of concepts employed precoordinated codes, 6% of guideline concepts required expanded vocabulary services employing Boolean logical definition using two or more SNOMED concepts. Postcoordination requirements were modest, representing just 6% of guideline semantic concepts. We conclude that creation of interoperable knowledge bases employing clinical vocabulary standards is achievable and realistic. Employment of information model (HL7 RIM) and vocabulary (SNOMED CT, LOINC) standards is a necessary and feasible requirement to achieve interoperability in clinical decision support.