There are several challenges in encoding guideline knowledge in a form that is portable to different clinical sites, including the heterogeneity of clinical decision support (CDS) tools, of patient data representations, and of workflows. We have developed a multi-layered knowledge representation framework for structuring guideline recommendations for implementation in a variety of CDS contexts. In this framework, guideline recommendations are increasingly structured through four layers, successively transforming a narrative text recommendation into input for a CDS system. We have used this framework to implement rules for a CDS service based on three guidelines. We also conducted a preliminary evaluation, where we asked CDS experts at four institutions to rate the implementability of six recommendations from the three guidelines. The experience in using the framework and the preliminary evaluation indicate that this approach has promise in creating structured knowledge, to implement in CDS systems, that is usable across organizations.