BACKGROUND: Large language models (LLMs), such as ChatGPT, excel at interpreting unstructured data from public sources, yet are limited when responding to queries on private repositories, such as electronic health records (EHRs). We hypothesized that prompt engineering could enhance the accuracy of LLMs for interpreting EHR data without requiring domain knowledge, thus expanding their utility for patients and personalized diagnostics. METHODS: We designed and systematically tested prompt engineering techniques to improve the ability of LLMs to interpret EHRs for nuanced diagnostic questions, referenced to a panel of medical experts. In 490 full-text EHR notes from 125 patients with prior life-threatening heart rhythm disorders, we asked GPT-4-turbo to identify recurrent arrhythmias distinct from prior events and tested 220 563 queries. To provide context, results were compared with rule-based natural language processing and BERT-based language models. Experiments were repeated for 2 ad