This FDA final guidance addresses the safe and effective interoperability of medical devices that connect and exchange information electronically (e.g., devices integrated with EHRs or connected to networks). It covers design considerations (risk management, error management, and data integrity), the technical documentation to include in premarket submissions, and labeling. It shows the correspondence with ISO 14971 (risk management). Essential reading for submissions of network-connected SaMD and medical IoT devices.