Hypertension and diabetes mellitus are the leading risk factors for cardiovascular diseases, which are increasing rapidly throughout the world. Hypertension is a non-communicable disease that remains a health problem in Indonesia, with a prevalence of up to 34.11% in 2018. This research was intended to identify cost-effective antihypertensive medication for inpatients with hypertension-diabetes mellitus and hypertensionheart failure. The research method used a retrospective cohort design and measured blood pressure (BP) 72 hours after treatment as the outcome of the observation. Based on a payer perspective, the medical expense was calculated from direct medical costs written in billing invoices. The research subjects were inpatients with hypertension-diabetes mellitus and hypertension-heart failure at a government hospital in Yogyakarta, Indonesia. In the cost-effectiveness analysis, Incremental Cost-Effectiveness Ratio (ICER) was calculated by dividing the difference in cost by the difference in the outcome of hypertension treatment.In the antihypertensive medication of hypertension-diabetes mellitus inpatients, angiotensin-receptor blockers/ calciumchannel blockers (ACB-CCB) were found to be more cost-effective than CCB with incremental costs of IDR 191,405/488,864 for every mmHg decrease of systolic/diastolic BP. Meanwhile, in the antihypertensive treatment of hypertension-heart failure inpatients, the combination of angiotensin-converting-enzyme inhibitors (ACEI) and diuretics was more cost-effective than ACEI-CCB (ICERs= IDR 8,303,483/-39,856,718 per mmHg) and ARB (ICERs= IDR 3,627,694/-2,380,075 per mmHg).In conclusion, ARB-CCB is a cost-effective medication for hypertension-diabetes mellitus inpatients, while ACEI-Diuretics offers a cost-effective hypertensive treatment for hypertension-heart failure inpatients.