Objectives: Comparative effectiveness research (CER) requires the capture and analysis of data from disparate sources, often from a variety of institutions with diverse electronic health record (EHR) implementations. In this paper we describe the CER Hub, a web-based informatics platform for developing and conducting research studies that combine comprehensive electronic clinical data from multiple health care organizations., Methods: The CER Hub platform implements a data processing pipeline that employs informatics standards for data representation and web-based tools for developing study-specific data processing applications, providing standardized access to the patient-centric electronic health record (EHR) across organizations., Results: The CER Hub is being used to conduct two CER studies utilizing data from six geographically distributed and demographically diverse health systems. These foundational studies address the effectiveness of medications for controlling asthma and the effectiveness of smoking cessation services delivered in primary care., Discussion: The CER Hub includes four key capabilities: the ability to process and analyze both free-text and coded clinical data in the EHR; a data processing environment supported by distributed data and study governance processes; a clinical data-interchange format for facilitating standardized extraction of clinical data from EHRs; and a library of shareable clinical data processing applications., Conclusion: CER requires coordinated and scalable methods for extracting, aggregating, and analyzing complex, multi-institutional clinical data. By offering a range of informatics tools integrated into a framework for conducting studies using EHR data, the CER Hub provides a solution to the challenges of multi-institutional research using electronic medical record data., (Copyright © 2015. Published by Elsevier Ireland Ltd.)