It is noticeable that, because of the amount and quality of information exchanged and the criticality of the decisions guided by them, hospitals are considered as some of the most complex organizations in modern society. Evidencing it, emergency departments in hospitals are examples of such complex environments that need perfect integration among systems, people, departments, and data. The processes behind the Emergency Department (ED) routine cause a set of critical and time-dependent decision-making, which must consider several criteria related to organizational and clinical attributes. Based on the literature and worldwide initiatives related to managing complex organizations, an ED can be interpreted through the enterprise interoperability (EI) lens, a concept related to the capability of different systems to work collaboratively within and throughout the organization. Thus, this paper proposes a framework focusing on interoperability assessment in ED processes, where different actors need to interoperate. The proposed framework for Enterprise Interoperability Assessment (EIA) is based on multicriteria decision analysis (MCDA) methods, considering organizational and clinical attributes of the ED. The Analytic Hierarchy Process (AHP) and Preference Ranking Organization Method for Enrichment Evaluation II (PROMETHEE II), in an integrated approach, were elected as the most appropriate multicriteria methods to support, respectively, diagnostic (interoperability assessment) and decisional (interoperability improvements) processes in this background. Last, to validate the framework proposed, a case study was carried out at a stroke unit in a University Hospital (UH) in the south of Brazil. The outcome inferred that the UH achieved the intermediate level of enterprise interoperability in stroke treatment, and Business and Information Technology concerns were found to be the priorities, which deserved greater efforts, to enhance interoperability.