Objective To investigate the variation of total hospitalization cost for single-diagnosed disease of different types of acute appendicitis in a three-A hospital, so as to provide evidence for the reimbursement amount of social medical insurance. Methods All patients with acute appendicitis who had surgery treatment during January-April 2011 (before implementing the fee system for single-diagnosed disease) and January-April 2012 (after implementing the fee system for single-diagnosed disease) were collected in this study for analysis. According to the types of acute appendicitis, the patients were stratified into the low risk group (simple, suppurative and gangrenous) and the high risk group (perforative, abscess-formed and pregnancy-combined). The correlation between total hospitalization cost and types of acute appendicitis, as well as the changes of total hospitalization cost after implementing the fee system for single-diagnosed disease were analyzed. Results A total of 90 eligible patients were included. The disease types were positively correlated with hospital stays and total hospitalization cost. All three types in the low risk group could control the average total hospitalization cost within RMB 10 000 yuan. The results of sensitivity analysis showed that, before implementing the fee system for single-diagnosed disease, the total hospitalization cost up to RMB 6 000 yuan could be positively correlated with the above risk stratification (r=0.442, P=0.003). After implementing the fee system for single-diagnosed disease from January to April 2012, the constituent ratio of hospital stays, compared with that in the same period of 2011, had no significant difference (P=0.108) between the two groups; but the ratio of hospital stays (less than 5 days) increased from 45% to 64%, and the ratio of hospital stays (greater than or equal to 10 days) decreased from 17% to 4%, indicating a tendency of shortening hospital stays. Also, the constituent ratio of total hospitalization cost had no significant difference (P=0.114) between the two groups; but the ratio of total hospitalization cost (greater than or equal to RMB 9 000 yuan) decreased from 32% to 13%, indicating a tendency of lowering total hospitalization cost. Conclusion The low risk group of acute appendicitis, RMB 6 000 yuan should be rated as the rational reimbursement amount of social medical insurance. The total hospitalization cost for the high risk group is quite various, so the further studies are needed to investigate the feasibility of the fee system for single-diagnosed disease as well as the rating amount of total hospitalization cost. The implementation of the fee system for single-diagnosed disease is helpful to shorten hospital stays and reduce total hospitalization cost.