Purpose: This study evaluates the accuracy of various large language models (LLMs) and compares them with radiologists in answering multiple-choice questions (MCQs) related to Prostate Imaging–Reporting and Data System version 2.1 (PI-RADSv2.1). Methods: This cross-sectional study utilizes one-hundred MCQs covering all sections of PI-RADSv2.1 were prepared and asked twelve different LLMs, including Claude 3 Opus, Claude Sonnet, ChatGPT models (ChatGPT 4o, ChatGPT 4 Turbo, ChatGPT 4, ChatGPT 3.5), Google Gemini models (Gemini 1.5 pro, Gemini 1.0), Microsoft Copilot, Perplexity, Meta Llama 3 70B, and Mistral Large. Two board-certified (EDiR) radiologists (radiologist 1,2) also answered the questions independently. Non-parametric tests were used for statistical analysis due to the non-normal distribution of data. Results: Claude 3 Opus achieved the highest accuracy rate (85%) among the LLMs, followed by ChatGPT 4 Turbo (82%) and ChatGPT 4o (80%), ChatGPT 4 (79%), Gemini 1.5pro (79%) both radiologists (79% each). There was no significant difference in performance among Claude 3 Opus, ChatGPT 4 models, Gemini 1.5 Pro, and radiologists (p > 0.05). Conclusion: The fact that Claude 3 Opus shows better results than all other LLMs (including the newest ChatGPT 4o) raises the question of whether it could be a new game changer among LLMs. The high accuracy rates of Claude 3 Opus, ChatGPT 4 models, and Gemini 1.5 Pro, comparable to those of radiologists, highlight their potential as clinical decision support tools. This study highlights the potential of LLMs in radiology, suggesting a transformative impact on diagnostic accuracy and efficiency. © Taiwanese Society of Biomedical Engineering 2024;