Objective To study the efficacy and safety of Yi Huo Hua Tan granule in the treatment of stable chronic obstructive pulmonary disease (COPD) patients with a traditional Chinese medicine (TCM) syndrome of Qi deficiency with phlegm and blood stagnation. Methods The stable COPD patients with a TCM syndrome of Qi deficiency with phlegm and blood stagnation who visited the outpatient in the Department of Integrated Traditional and Western Medicine, West China Hospital of Sichuan University between August 2016 and March 2017 were selected. The patients were randomly divided into an experimental group and a control group using a random number table method. Patients in both groups received conventional western medicine, with Yi Huo Hua Tan granule being additionally prescribed in patients in the experimental group. The treatment during was 60 days. The TCM effective rate, TCM syndrome score, COPD Assessment Test (CAT) score, modified Medical Research Council Dyspnea Scale, six minutes walking distance, long-term prognostic indicators, lung function indicators, inflammatory cytokines in serum and induced sputum supernatant were compared between groups. The safety of Yi Huo Hua Tan granule was also observed. Results A total of 69 patients were included, including 34 patients in the experimental group and 35 patients in the control group. After treatment of Yi Huo Hua Tan granule for 2 months , the total effective rate of TCM syndrome was 44.1% and 8.6% in the experimental group and the control group, respectively (P=0.001). There were statistically significant differences at 2 months and 4 months of follow-up visits between groups (P<0.05). After 2 months treatment, TCM syndrome score, CAT score, modified Medical Research Council score, number of acute exacerbations per year, hospitalization per year, and total length of hospital stay per year in the experimental group were lower than those in the control group (P<0.05). The six minutes walking distance, forced vital capacity, forced expiratory volume in one second, forced expiratory volume in one second /predicted value, serum, and the concentrations of interleukin (IL)-6, IL-1β, and IL-10 in induced sputum supernatant between the two groups showed no statistically significant difference (P>0.05). There was no significant change in blood routine, liver and kidney function, electrocardiogram, or urine and urine routine of the patients in the two groups. Conclusion Yi Huo Hua Tan granule improves the clinical symptoms and quality of life in patients with stable COPD, with a good safety.