Objective: The paper analyzes the DRG payment results grouped according to the main diagnosis categories (MDC), and provides reference for the optimization of the disease structure of medical institutions and their refined management of medical insurance funds. Methods: The first page of medical records, grouping results, medical insurance settlement and DRG payment data of cases paid by DRG in a large tertiary general hospital of Shandong Province in 2022 was obtained, and the payment results of DRG by MDC were analyzed by descriptive statistics. Results: In 2022, a total of 144158 cases paid by DRG was distributed in 26 MDCs, among which the top three were MDCR, MDCB and MDCF. There were 14 MDCs whose average weight was higher than the theoretical weight, accounting for 53.85%, and 12 MDCs whose average weight was lower than the theoretical weight, accounting for 46.15%. In terms of payment rate, the top three were MDCY, MDCR and MDCI (140.56%, 124.83% and 119.85%), and the last three were MDCA, MDCW and MDCO (75.53%, 75.92% and 78.04%). There were differences in cost distribution, weight and payment results of cases grouped according to MDC. Conclusion: The distribution of diseases admitted by hospitals is related to the incidence of disease in each MDC and the development of hospital disciplines. The analysis of MDC can provide a basis for adjusting the disease structure of medical institutions and optimizing medical insurance payment policies.