Abstract: Objective To compare the efficacy and safety of reserpine and triamterene compound tablets（antihypertensive No.0）with indapamide in high-risk patients with mild to moderate essential hypertension. Methods This was a multicenter,cluster randomized,active-controlled and prospective clinical trial. Hypertensive patients were enrolled from 13 hospitals in 10 regions throughout the country between January 2003 and December 2005,and were followed up for 2years. The efficacy and safety of antihypertensive No.0（1tablet per day）and indapamide（2.5mg/d）were evaluated. Results A total of 4062 patients with essential hypertension from different regions were enrolled.There were 2324 patients in the antihypertensive No.0group and 1738 patients in the indapamide group. After 2-year treatment and followed-up,A decrease in the systolic blood pressure in the both groups,but there was no significant difference in the degree of the decrease between the two groups（30.2±17.2）vs（29.1±19.6）mm Hg,P=0.053. The control rates of blood pressure was higher in the antihypertensive No.0group than in the indapamide group（62.6% vs 56.6%,P＜0.05）. The incidence rates of hypokalemia（1.8% vs 3.5%）,increased serum creatinine（49.5% vs 61.1%）and increased serum uric acid（50.2% vs 57.2%）were lower in the antihypertensive No.0group than in the indapamide group（all P＜0.05）. The incidence rates of drug-related adverse events or possibly related adverse events was lower in the antihypertensive No.0group than in the indapamide group（2.45% vs 3.22%,P=0.046）. The incidence rates of cardiovascular and cerebrovascular events was 0.38% and0.46%in the two groups,respectively. Conclusion Both antihypertensive No.0and indapamide were safe and effective in high-risk patients with mild to moderate hypertension,and were suitable for long-term use in primary hospitals,while antihypertensive No.0had a lower risk of hypokalemia.