Objective: 1) To compare the efficacy of two drugs, Amlodipine and hydrochlorothiazide (HCTZ), in elderly Thai patients with isolated systolic hypertension (ISH) in terms of regression of left ventricular hypertrophy (LVH) and blood pressure control. 2) To detect the short (six months) and medium (18 months) terms of clinical outcomes of major cardiovascular events, i.e., congestive heart failure (CHF), myocardial infarction (MI), cerebrovascular disorders (CVD), death and minor clinical outcomes or adverse drug effects. This is a prospective randomized control study. Methods: From October 1997 to March 2000, 200 elderly patients with ISH, mean age of 69.3 years, were randomized into two groups, to receive either Amlodipine or HCTZ as a primary drug. Their baseline clinical data, blood chemistry, ECG, and echocardiography (ECHO) were evaluated. Regression of LVH was re-examined at six months; BP measurement was measured every 3 months for 18 months; and, clinical outcomes were followed at the end of study. Clinical end points were defined as death, myocardial infarction, and congestive heart failure. Results: Sixty-six percent of all patients had LVH by the ECHO criteria. After six months of monotherapy, there was regression of LVH in both groups (p < 0.01), but no difference in the reduction of LVMI between the two groups (p = 0.33). There was a significant reduction in BPsys in both treatment groups (p < 0.01). Those who received Amlodipine had more frequent side effects and were withdrawn from the study (p =0.02). The major adverse drug effect was leg edema (Amlodipine). However, more patients in the HCTZ group required additional drugs (Prazosin) in order to control BP to the desired level (39.2% vs 14.5%, p < 0.001). There was no statistical difference in clinical end points during follow-up. Difference of total drugs costs for one year of treatment was 8,084 Baht/patient in favor of the HCTZ regimen. Conclusion: It is suggested that a low dose of the HCTZ regimen is more cost effective when compared with Amlodipine and should be considered as the first antihypertensive agent of choice for ISH in the Thai elderly.