The adoption of health information technology (HIT) has facilitated efforts to increase the quality and efficiency of health care services and decrease health care overhead while simultaneously generating massive amounts of digital information stored in electronic health records (EHRs). However, due to patient safety issues resulting from the use of HIT systems, there is an emerging need to develop and implement hazard detection tools to identify and mitigate risks to patients. This paper presents a new methodological framework to develop hazard detection models and to demonstrate its capability by using the US Department of Veterans Affairs’ (VA) Corporate Data Warehouse, the data repository for the VA’s EHR. The overall purpose of the framework is to provide structure for research and communication about research results. One objective is to decrease the communication barriers between interdisciplinary research stakeholders and to provide structure for detecting hazards and risks to patient safety introduced by HIT systems through errors in the collection, transmission, use, and processing of data in the EHR, as well as potential programming or configuration errors in these HIT systems. A nine-stage framework was created, which comprises programs about feature extraction, detector development, and detector optimization, as well as a support environment for evaluating detector models. The framework forms the foundation for developing hazard detection tools and the foundation for adapting methods to particular HIT systems.