Background: With the widespread use of electronic health records (EHRs) for many clinical tasks, interoperability with other health information technology (health IT) is critical for the effective delivery of care. While it is generally recognized that poor interoperability negatively impacts patient care, little is known about the specific patient safety implications. Understanding the patient safety implications will help prioritize interoperability efforts around architectures and standards. Objectives: Our objectives were to (1) identify patient safety incident reports that reflect EHR interoperability challenges with other health IT, and (2) perform a detailed analysis of these reports to understand the health IT systems involved, the clinical care processes impacted, whether the incident occurred within or between provider organizations, and the reported severity of the patient safety events. Methods: From a database of 1.735 million patient safety event (PSE) reports spanning multiple provider organizations, 2625 reports that were indicated as being health IT related by the event reporter were reviewed to identify EHR interoperability related reports. Through a rigorous coding process 209 EHR interoperability related events were identified and coded. Results: The majority of EHR interoperability PSE reports involved interfacing with pharmacy systems (i.e. medication related), followed by laboratory, and radiology. Most of the interoperability challenges in these clinical areas were associated with the EHR receiving information from other health IT systems as opposed to the EHR sending information to other systems. The majority of EHR interoperability challenges were within a provider organization and while many of the safety events reached the patient, only a few resulted in patient harm. Conclusions: Interoperability efforts should prioritize systems in pharmacy, laboratory, and radiology. Providers should recognize the need to improve EHRs interfacing with other health IT systems within their own organization.