Objective: Although social and environmental factors are central to provider-patient interactions, the data that reflect these factors can be incomplete, vague, and subjective. We sought to create a conceptual framework to describe and classify data about presence, the domain of interpersonal connection in medicine. Methods: Our top-down approach for ontology development based on the concept of "relationality"included the following: 1) a broad survey of the social sciences literature and a systematic literature review of >20 000 articles around interpersonal connection in medicine, 2) relational ethnography of clinical encounters (n = 5 pilot, 27 full), and 3) interviews about relational work with 40 medical and nonmedical professionals. We formalized the model using the Web Ontology Language in the Protégé ontology editor. We iteratively evaluated and refined the Presence Ontology through manual expert review and automated annotation of literature. Results and Discussion: The Presence Ontology facilitates the naming and classification of concepts that would otherwise be vague. Our model categorizes contributors to healthcare encounters and factors such as communication, emotions, tools, and environment. Ontology evaluation indicated that cognitive models (both patients' explanatory models and providers' caregiving approaches) influenced encounters and were subsequently incorporated. We show how ethnographic methods based in relationality can aid the representation of experiential concepts (eg, empathy, trust). Our ontology could support investigative methods to improve healthcare processes for both patients and healthcare providers, including annotation of videotaped encounters, development of clinical instruments to measure presence, or implementation of electronic health record-based reminders for providers. Conclusion: The Presence Ontology provides a model for using ethnographic approaches to classify interpersonal data.