Measuring healthcare acceptability presents conceptual and contextual challenges, particularly in data-poor Multi-Island Microstates (MIMS). Thus, there has been limited evidence on acceptability of healthcare in MIMS, and scarce use of acceptability metrics in policy design and health system evaluation. In the present study, we developed and empirically validated a theoretical framework for measuring users’ acceptability of healthcare in a Multi-Island Microstate in the Caribbean. Using a minimum-data approach, we used synoptic review of healthcare literature and consultations with experts and health system stakeholders to define, scope and select constructs for the theoretical framework of healthcare acceptability. Empirical validation of the modelled framework was performed using data collected from household expenditure and healthcare utilization surveys in Carriacou and Petite Martinique (n = 226), island dependents of Grenada in the Caribbean. Data were used to create health utilization profiles and analyse measurement scales of the healthcare acceptability framework using non-linear partial-least square structural equation modelling. The modelled framework included 17-items integrating economic and psychosocial concepts, with one dependent construct (utilization) and 3 independent constructs (users’ perception, experience, and knowledge of health facility). Model analysis and validation indicated that the framework was significant, explaining 19% of the variation in healthcare acceptability. Users’ experience construct was influenced by perception and knowledge of health facility, and was the only construct with a significant negative relationship with acceptability. Healthcare acceptability declined with increased waiting and travel times, and unsuitable opening hours. We conclude that acceptability comprises of a complex multidimensional concept, which is highly dependent on various interacting variables and contextual characteristics of the health system. Therefore, policies and actions to improve acceptability should be context specific and focused on evaluating factors infringing healthcare acceptability. Routine acceptability and/or satisfaction studies represent baseline evidence towards understanding and integrating acceptability in healthcare assessment.