OBJECTIVES: Widespread adoption of electronic health records (EHRs) results in a wealth of data in structured/codified and unstructured/uncodified electronic formats.  Research studies seeking to use these data require translation of narrative research protocols into EHR-friendly queries.  This involves interpretation of the protocols, distillation into distinctive query-level components and determination of appropriate code value sets (list of ICD-9 codes, procedure codes, medication codes, etc.).  In addition, for studies conducted across multiple disparate EHR data sources, it is essential to ensure queries are conducted in a consistent and comparable manner.  EHR-friendly query definitions provide the necessary granularity of information needed to conduct consistent queries across multiple EHR data sources.  The objective is to develop and demonstrate the value of a curated EHR research query definition library to improve efficiency of EHR research queries. METHODS: A standard format for electronic research query definitions was established following federal EHR certification standards.  A logic format was developed to articulate the research protocol into informaticist terms that lead to data analyst-friendly query statements. Healthcare industry standard vocabulary terminologies are used to develop code value sets.  A hosting library was developed to maintain version control and repurposing of developed definitions. RESULTS: Our query definition format, content and time-savings were validated through an iterative process with multiple healthcare informatics systems across a variety of disease therapy areas, including but not limited to: cardiovascular, CNS/neurology, metabolics, nephrology, oncology, pulmonology/respiratory, etc. CONCLUSIONS: An EHR-compatible format for research query definitions expedites the process of data query and analysis.  Our Query Definition Library of protocol-specific validated query definitions standardizes queries and expedites future definition development.  It also provides ready access to curated standardized EHR-compatible research query definitions to support clinical research studies.