Preventable medical errors represent a major public health problem. To prevent future errors, improve disclosure, and mitigate malpractice risks, organizations have adopted strategies for transparent communication and emphasized quality improvement through peer review. These principles are incorporated into the Agency for Healthcare Research and Quality (AHRQ) Communication and Optimal Resolution (CANDOR) Toolkit, which facilitates (1) transparent communication, (2) error prevention, and (3) achieving optimal resolution with patients and families; however, how medical errors should be addressed when they are discovered between systems-intersystem medical error discovery (IMED)-remains unclear. Without mechanisms for disclosure and feedback on the part of the discovering provider, uncertainty remains as to the extent to which IMED is communicated with patients or responsible providers. Furthermore, known barriers to disclosure and reporting one's own error may not be relevant or may be replaced by other unknown barriers when considering scenarios of IMED. This study aims to develop and test implementation of a modified CANDOR process for application to IMED scenarios. We plan a series of studies following an implementation framework. First, we plan a participatory, consensus-building stakeholder panel process to develop the modified CANDOR process. We will then conduct a robust preimplementation analysis to identify determinants of implementation of the modified process. Using the Consolidated Framework for Implementation Research as a theoretical framework, we will assess organizational readiness by key informant interviews and individual-level behaviors by a survey. Findings from this analysis will inform the implementation toolkit that will be developed and pilot-tested at 2 cancer centers, sites where IMED is hypothesized to occur more frequently than other settings. We will measure 5 implementation outcomes (acceptability, appropriateness, reach, adoption, and feasibility) using a combination of key informant interviews and surveys over the pre- and postimplementation phases. This protocol was funded in August 2018 with support from the AHRQ. The University of Michigan Medical School Institutional Review Board has reviewed and approved the scope of activities described. As of April 2019, step 1 of aim 1 is underway, and aim 1 is projected to be completed by April 2020. Data collection is projected to begin in January 2020 for aim 2 and in August 2020 for aim 3. Providing a communication and resolution strategy applicable to IMED scenarios will help address the current blind spot in the patient safety movement. This work will provide important insights into the potential utility of an implementation toolkit to improve transparent communication and optimal resolution of IMED scenarios. The natural progression of this work will be to test the toolkit more broadly, understand the feasibility and barriers of implementation on a broader scale, and pilot the implementation in new organizations. PRR1-10.2196/13396. ©Lesly Dossett, Jacquelyn Miller, Reshma Jagsi, Anne Sales, Michael D Fetters, Richard C Boothman, Justin B Dimick. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 02.07.2019.