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BACKGROUND Health systems have recently started to activate patient-facing application programming interfaces (APIs) to facilitate patient access to health data and other interactions. OBJECTIVE This study sought to ascertain health systems' understanding, strategies, governance, and organizational infrastructure around patient-facing APIs, as well as their business drivers and barriers, to facilitate national learning, policy, and progress toward adoption. METHODS We performed content analysis of semi-structured interviews with a convenience sample of 10 health systems known to be leading adopters of health technology, having either implemented or planning to implement patient-facing APIs. RESULTS Eight of the ten health systems had operational patient-facing APIs, with organizational strategy driven most by federal policy, the emergence of Apple Health Records, and feelings of ethical obligation. The two priority use cases identified were enablement of a patient's longitudinal health record and digital interactions with the health system. The themes most frequently cited as barriers to increased use of patient-facing APIs were security concerns, an immature app ecosystem that does not currently offer superior functionality compared to widely-adopted electronic health record (EHR)-tethered portals, lack of business drivers, EHR-vendor hesitation toward data sharing, and immature technology and standards. CONCLUSIONS Our findings reveal heterogeneity in health system understanding and approaches to implementation and use of patient-facing APIs. Ongoing study, targeted policy interventions, and sharing of best practices appear necessary to achieve successful national implementation. CLINICALTRIAL