Objective. To discuss the effect of clinical pathway single disease quota payment mode on medical costs. Methods. Collecting the total cost, drug costs, and inspection fee details of gallbladder benign disease surgery, acute simple appendicitis operation, planned cesarean section during 2009 and 2011 in Qianjiang Central Hospital; and analyzing the treatment costs of single diseases before and after clinical pathway single diseases implementation using spss11.0. Results. Compared to the medical costs incurred prior to clinical pathway single disease management, there was a dramatic decline in the total cost and the drug expenses incurred on gallbladder benign disease surgery, appendicitis operation, and cesarean section. There was a significant difference of P < 0.05. The consultation fees of gallbladder benign disease surgery and cesarean section were lower, with no significant difference (P > 0.05). The consultation fee of cesarean section was increased, with a significant difference of P < 0.05. Conclusion. It can reduce the total cost incurred on the disease and the drug fees, reduce the health-care costs, curb the growth of unreasonable medical expenses, and reduce the wastage of health resources.