Long-term institutional care in the United Kingdom is provided by care homes. Residents have prevalent cognitive impairment and disability, have multiple diagnoses, and are subject to polypharmacy. Prevailing models of health care provision (ad hoc, reactive, and coordinated by general practitioners) result in unacceptable variability of care. A number of innovative responses to improve health care for care homes have been commissioned. The organization of health and social care in the United Kingdom is such that it is unlikely that a single solution to the problem of providing quality health care for care homes will be identified that can be used nationwide. Realist evaluation is a methodology that uses both qualitative and quantitative data to establish an in-depth understanding of what works, for whom, and in what settings. In this article we describe a protocol for using realist evaluation to understand the context, mechanisms, and outcomes that shape effective health care delivery to care home residents in the United Kingdom. By describing this novel approach, we hope to inform international discourse about research methodologies in long-term care settings internationally.