Introduction:Medical care for patients with diabetes mellitus type 2 is expensive,particularly in the presence of complications. Indeed, in the era of the National Health Security Program the effectiveness and efficiency of medical care provision has been regarded paramount.This study aimed to identify the differenceof cost-effectivenessamong the prescription of oral antidiabetic therapy, oral and oral, insulin, oral and insulin, and oral, oral, and insulin. Methods: This study was a retrospective study utilizing the outpatientsmedical record of self paid participant of NSS in a hospital in Yogyakarta diagnosed with type 2 diabetes mellitus. Results: there are three types of antidiabetic drugs which have minus values in the ICER, namely Sulfonylureas, the combination of Biguanides, Sulfonylureas, andThiazolindinedione, and the combination of Sulfonylureas andBiguanides. Conclusion: the combination of Sulfonylureas and Biguanides,which is a combination of oral and oral antidiabetic therapy, is the most costeffectivemedication with the ICER (Incremental Cost-Effectiveness Ratio) values ofRp -170,2081 Keywords: Cost-Effective, ICER