Background: The rapid digitalization of healthcare has intensified the need for Electronic Health Record (EHR) interoperability to ensure seamless, secure, and meaningful data exchange among health systems. Interoperability enhances coordination, reduces redundancies, and promotes patient-centered care; however, challenges persist in usability, data quality, and standardization.

Objective: This systematic review aimed to synthesize empirical evidence on the impact of EHR interoperability and Health Information Exchange (HIE) on patient data sharing, safety, and healthcare outcomes across different settings.

Methods: Following PRISMA 2020 guidelines, ten peer-reviewed studies (2010– 2024) were included through searches in PubMed, Scopus, Embase, Web of Science, and IEEE Xplore. Eligible studies evaluated interoperability or HIE effects on efficiency, readmissions, safety, or data completeness. Data were narratively synthesized due to heterogeneity.

Results: Across included studies, interoperability improved efficiency (e.g., faster information retrieval by 58.5 minutes per patient encounter), reduced duplicate imaging by 64%, and lowered readmissions by up to 57%. Patient safety and continuity improved through shared inpatient–outpatient EHRs and blockchain-based systems. Barriers included fragmented standards, limited usability, and cost burdens, especially in small or resource-limited hospitals.

Conclusions: EHR interoperability positively influences patient data exchange and outcomes by fostering timeliness, quality, and continuity of care. Nonetheless, persistent structural and usability barriers require targeted policy, financial, and design interventions. Future research should emphasize interoperability equity and cross- system scalability.