Interest in application programming interfaces (APIs) is increasing as key stakeholders look for technical solutions to interoperability challenges. We explored three thematic areas to assess the current state of API use for data access and exchange in health care: (1) API use cases and standards; (2) challenges and facilitators for read and write capabilities; and (3) outlook for development of write capabilities. We employed four methods: (1) literature review; (2) expert interviews with 13 API stakeholders; (3) review of electronic health record (EHR) app galleries; and (4) a technical expert panel. We used an eight-dimension sociotechnical model to organize our findings. The API ecosystem is complicated and cuts across five of the eight sociotechnical model dimensions: (1) app marketplaces support a range of use cases, the majority of which target providers' needs, with far fewer supporting patient access to data; (2) current focus on read APIs with limited use of write APIs; (3) where standards are used, they are largely Fast Healthcare Interoperability Resources (FHIR); (4) FHIR-based APIs support exchange of electronic health information within the common clinical data set; and (5) validating external data and data sources for clinical decision making creates challenges to provider workflows. While the use of APIs in health care is increasing rapidly, it is still in the pilot stages. We identified five key issues with implications for the continued advancement of API use: (1) a robust normative FHIR standard; (2) expansion of the common clinical data set to other data elements; (3) enhanced support for write implementation; (4) data provenance rules; and (5) data governance rules. Thus, while APIs are being touted as a solution to interoperability challenges, they remain an emerging technology that is only one piece of a multipronged approach to data access and use.