Electronic health record (EHR)-based interventions to improve patient safety are complex and sensitive to who, what, where, why, when, and how they are delivered. Success or failure depends not only on the characteristics and behaviors of individuals who are targeted by an intervention, but also on the technical characteristics of the intervention and the culture and environment of the health system that implements it. Current reporting guidelines do not capture the complexity of sociotechnical factors (technical and nontechnical factors, such as workflow and organizational issues) that confound or influence these interventions. This article proposes a methodological reporting framework for EHR interventions targeting patient safety and builds on an 8-dimension sociotechnical model previously developed by the authors for design, development, implementation, use, and evaluation of health information technology. The Safety-related EHR Research (SAFER) Reporting Framework enables reporting of patient safety-focused EHR-based interventions while accounting for the multifaceted, dynamic sociotechnical context affecting intervention implementation, effectiveness, and generalizability. As an example, an EHR-based intervention to improve communication and timely follow-up of subcritical abnormal test results to operationalize the framework is presented. For each dimension, reporting should include what sociotechnical changes were made to implement an EHR-related intervention to improve patient safety, why the intervention did or did not lead to safety improvements, and how this intervention can be applied or exported to other health care organizations. A foundational list of research and reporting recommendations to address implementation, effectiveness, and generalizability of EHR-based interventions needed to effectively reduce preventable patient harm is provided. The SAFER Reporting Framework is not meant to replace previous research reporting guidelines, but rather provides a sociotechnical adjunct that complements their use.