This study aimed to investigate the curative effect of Yiqi Huoxue Tongmai decoction on In-Stent Restenosis (ISR) after Percutaneous Coronary Intervention (PCI) in Coronary Heart Disease (CHD). 95 cases of patients with ISR after PCI due to CHD were randomly divided into control group (46 cases) and Traditional Chinese Medicine (TCM) group (49 cases) who received conventional Western medicine therapy and therapy with Yiqi Huoxue Tongmai decoction based on conventional Western medicine therapy, respectively. After 12 months of treatment, the clinical efficacy, symptom scores, Electrocardiogram (ECG), coronary angiography, biochemical indexes in two groups were observed. Results showed that, the total clinical effective rate and total effective rate by ECG in TCM group were significantly higher than control group (P<0.05). After treatment, the scores of chest pain, chest tightness, fatigue and dry mouth in TCM group were significantly lower than control group, respectively (P<0.05); the ISR rate in TCM group was significantly lower than control group (P<0.05); the blood lipid levels in TCM group were also significantly lower than those in control group (P<0.05). Yiqi Huoxue Tongmai decoction has obvious curative effect on ISR after PCI in CHD patients, with no obvious adverse side effect.