Abstract
BACKGROUND: Large language models such as ChatGPT (OpenAI) have shown promise in medical education assessments, but the comparative effects of prompt engineering across optimized variants and relative performance against medical students remain unclear. OBJECTIVE: This study aims to systematically evaluate the impact of prompt engineering on five ChatGPT variants (GPT-3.5, GPT-4.0, GPT-4o, GPT-4o1-mini, and GPT-4o1) and benchmark their performance against fourth-year medical students in midterm and final examinations. METHODS: A 100-item examination dataset covering multiple choice questions, short answer questions, clinical case analysis, and image-based questions was administered to each model under no-prompt and prompt-engineering conditions over 5 independent runs. Student cohort scores (N=143) were collected for comparison. Responses were scored using standardized rubrics, converted to percentages, and analyzed in SPSS Statistics (v29.0) with paired t tests and Cohen d (P<.05). RESULTS: Baseline midterm scores ranged from 59.2% (GPT-3.5) to 94.1% (GPT-4o1), and final scores ranged from 55% to 92.4%. Fourth-year students averaged 89.4% (midterm) and 80.2% (final). Prompt engineering significantly improved GPT-3.5 (10.6%, P<.001) and GPT-4.0 (3.2%, P=.002) but yielded negligible gains for optimized variants (P=.07-.94). Optimized models matched or exceeded student performance on both exams. CONCLUSIONS: Prompt engineering enhances early-generation model performance, whereas advanced variants inherently achieve near-ceiling accuracy, surpassing medical students. As large language models mature, emphasis should shift from prompt design to model selection, multimodal integration, and critical use of artificial intelligence as a learning companion.