OBJECTIVES: Resistant hypertension (RH) is highly associated with cardiovascular risks. The difficulty in enrolling large numbers of study participants limits studies on treatment effects of RH. This study aims to compare the effectiveness of triple antihypertensive combination therapy for RH patients in Taiwan. METHODS: Patients who had 3 antihypertensive agents of different classes concurrently prescribed in outpatient clinics with their medication possession ratio ≧0.7 during 2004-2006 were identified as the RH cases from the National Health Insurance Research database. The 1^st outpatient visit with 3 antihypertensive agents of different classes being prescribed was defined as the index date. Patients were further classified into two treatment groups according to the combination of antihypertensive therapy; the A+B+C group was defined as those who received concurrent therapy of ACEI/ARB in combination with beta-blocker and CCB, and the A+C+D group was those who received ACEI/ARB together with CCB and diuretics. The Cox proportional regression analysis was performed to investigate the risk of major adverse cardiovascular events (MACE) between the two treatment groups. Subgroup analysis was further performed by classifying patients into those with or without previous history of stroke, myocardial Infarction or end stage renal diseases. RESULTS: There were 13,551 patients identified as the prevalence cases of RH during 2004-2006. Results showed the A+C+D group had a lower risk of MACE  when compared to the A+B+C of group (adjusted HR=1.11; 95%CI 1.01-1.22; p=0.0272). Subgroup analysis showed there was no significant difference in the risk of MACE between the A+B+C and the A+C+D groups either in patients with prior disease history (adjusted HR =1.10; 95%CI 0.96-1.25; p=0.1881) or without prior disease history (adjusted HR =1.12; 95%CI 0.99-1.28; p=0.0767). CONCLUSIONS:  The A+C+D combination therapy seemed to be more effective than the A+B+C therapy in preventing MACE among patients with RH.