This FDA final guidance addresses design and regulatory considerations for medical devices that communicate electronically with other devices, health information systems, or electronic health records (EHR). The document emphasizes that interoperable devices must maintain safety and effectiveness across diverse clinical environments and integration scenarios. Manufacturers should incorporate risk management per ISO 14971 to identify and mitigate hazards associated with data exchange, system interoperability, and information integrity. Key design considerations include error detection and correction mechanisms, data validation and reconciliation procedures, interface standardization (HL7, DICOM, or equivalent standards), and cybersecurity protections ensuring confidential and accurate information exchange. Premarket submissions for interoperable devices must include technical documentation describing data exchange protocols, interface specifications, validation testing demonstrating accurate data transmission and receipt, and labeling clearly defining compatible systems and valid use cases. The guidance establishes that interoperability requirements should be addressed through systematic design controls incorporating software development processes per IEC 62304 where applicable. Manufacturers should validate interoperability across representative healthcare information technology environments. The guidance recognizes that interoperable devices create complex system-level risks requiring comprehensive validation approaches extending beyond individual device testing.