Retrieval-Augmented Generation (RAG) in Healthcare: A Comprehensive Review

Retrieval-Augmented Generation (RAG) enhances large language models (LLMs) by integrating external knowledge retrieval to improve factual consistency and reduce hallucinations. Despite growing interest, its use in healthcare remains fragmented. This paper presents a Systematic Literature Review (SLR) following PRISMA guidelines, synthesizing 30 peer-reviewed studies on RAG in clinical domains, focusing on three of its most prevalent and promising applications in diagnostic support, electronic health record (EHR) summarization, and medical question answering. We synthesize the existing architectural variants (naïve, advanced, and modular) and examine their deployment across these applications. Persistent challenges are identified, including retrieval noise (irrelevant or low-quality retrieved information), domain shift (performance degradation when models are applied to data distributions different from their training set), generation latency, and limited explainability. Evaluation strategies are compared using both standard metrics and clinical-specific metrics, FactScore, RadGraph-F1, and MED-F1, which are particularly critical for ensuring factual accuracy, medical validity, and clinical relevance. This synthesis offers a domain-focused perspective to guide researchers, healthcare providers, and policymakers in developing reliable, interpretable, and clinically aligned AI systems, laying the groundwork for future innovation in RAG-based healthcare solutions.