OBJECTIVE: To investigate the efficacy and safety of Angong Jiangya pill (AGJY, ) in the treatment of grade 2 hypertension with liver-fire hyperactivity syndrome. METHODS: This multicenter, randomized, double-blind, placebo-controlled trial was conducted in eight medical institutions. Eligible patients with grade 2 hypertension were randomly allocated to receive AGJY or a placebo for 12 weeks. The primary outcome was the change in blood pressure (BP). The secondary outcomes were BP compliance rate, Traditional Chinese Medicine (TCM) symptoms, and Duchenne Hypertension Quality of Life Scale score. RESULTS: Data were analyzed for 117 participants in the AGJY group and 118 participants in the placebo group. After 12 weeks of treatment, AGJY compared with placebo resulted in a higher and significant reduction in systolic/diastolic BP (－15.58 ± 10.16/－9.72 ± 7.41 CONCLUSION: AGJY demonstrated efficacy in lowering BP, increasing the rate of BP compliance, and improving TCM symptoms and quality of life in patients with grade 2 hypertension liver-fire hyperactivity syndrome. However, further in-depth studies are required to determine the mechanism of TCM in treating hypertension.