MACD: Multi-Agent Clinical Diagnosis with Self-Learned Knowledge for LLM

Large language models (LLMs) have shown promise in supporting medical diagnosis, with prompting-based methods offering a flexible and deployable means of capability enhancement. However, existing prompt engineering and multi-agent approaches often focus on optimizing single inferences, paying less attention to the accumulation of reusable experience from clinical practice, constraining their real-world applicability. To address this, this study proposes a novel Multi-Agent Clinical Diagnosis (MACD) framework, which allows LLMs to self-learn clinical knowledge via a multi-agent pipeline that summarizes, refines, and applies diagnostic insights, mirroring the professional development of human physicians. We further extend it to a MACD-human collaborative workflow, where multiple LLM-based diagnostician agents engage in iterative consultations, supported by a judge agent and human oversight for cases where agreement is not reached. The MIMIC-MACD cohort comprising 4,390 real-world patient cases across seven diseases is constructed, including 1,314 cases for knowledge learning and 3,076 held-out cases for evaluation. Across diverse open-weight LLMs, MACD significantly improves primary diagnostic accuracy, achieving an average improvement of 11.6 percentage points over established authoritative knowledge, while narrowing the performance gap between open-weight models and state-of-the-art LLMs. Furthermore, the MACD-human workflow yields an 18.3-percentage-point improvement over physician-only diagnosis on text-only vignettes, demonstrating the synergistic potential of human-AI collaboration. This work thus presents a scalable self-learning paradigm that bridges the gap between the intrinsic knowledge of LLMs and the demands of real-world clinical practice, advancing towards a reliable, interpretable, and deployable AI-assisted diagnosis.