Objective To elaborate on the statistical analysis methods for evaluating the accuracy of imaging diagnostic tests in a multiple-reader multiple-case (MRMC) design through formula derivation and real cases. Methods This study consisted of two parts: theoretical derivation and a real case study. The theoretical part discussed in detail the principles and procedures of MRMC statistical analysis methods, particularly the Obuchowski-Rockette (OR) and Dorfman-Berbaum-Metz (DBM) methods. The real case included 100 subjects, of whom 67 had disease. Four readers interpreted all the cases based on both traditional film imaging methods and digital imaging methods. OR and DBM methods were employed for data analysis. Results The real case showed that the OR and DBM methods had a high degree of consistency, with only slight differences in the confidence intervals. Conclusion It is recommended to use the OR and DBM methods for the statistical analysis of imaging diagnostic test accuracy, ensuring that the impact of reader factors on the evaluation results is fully considered. The results from the OR and DBM methods are relatively similar; when applying these methods in practice, one should consider the specific characteristics of the data and the research design to choose the appropriate analysis method. Besides, there are still challenges when applying the OR and DBM methods, such as software implementation and missing data handling, which require further exploration.