OBJECTIVE To investigate the clinical efficacy of aspirin combined with Huoxue Quyu decoction in the treatment of lower extremity arteriosclerosis obliterans (ASO). METHODS A total of 136 patients with lower extremity ASO admitted to our hospital were selected as the research objects, aged 49-87 years, with an average age of (65.00±6.54) years. According to treatment methods, 68 cases of conventional aspirin treatment were included in the control group, and 68 cases of Huoxue Quyu prescription combined with aspirin were included in the study group. The platelet function, hemodynamic index, blood lipid index, arteriosclerosis index, health status and clinical effect of the two groups were compared before and after treatment. Generalized estimation equation (GEE) model was used to analyze the factors affecting the clinical efficacy of ASO in the lower extremities, and GEE model was used to analyze the interaction effects of ankle-brachial index(ABI) at different time points, different groups and different stages. RESULTS After 6 weeks of treatment, the platelet function, hemodynamic indexes, lipid indexes and arteriosclerosis indexes of the two groups were significantly different compared with those before treatment (P<0.05). PAR, D-D, FIB, HWBV, LWBV, ESR, TC, TG and LDL-C levels in the study group were significantly lower than those in the control group (P<0.05), while BT, HDL-C, ABI, TBI, lameness distance, health status score and clinical efficacy were significantly higher than those in the control group (P<0.05). GEE model analysis showed that treatment method, treatment time and Fontaine stage significantly affected the therapeutic effect of ASO in lower limbs (P<0.05). In the interaction effect analysis, after 2 and 4 weeks of treatment, the ABI values of ASO patients in the study group and the control group were significantly different (P<0.05). After 6 weeks of treatment, different treatment methods had statistically significant effects on ABI values of ASO patients in stage Ⅱ, Ⅲ and Ⅳ (P<0.05). CONCLUSION Aspirin combined with Huoxue Quyu decoction is better than aspirin alone in the treatment of lower extremity ASO in the aspect of improvement of platelet function, hemodynamics, blood lipids and arteriosclerosis. After 6 weeks of treatment, the total effective rate and health status SF-36 score of the study group with combined medication are significantly higher than those of the control group. Treatment method, treatment time and Fontaine stage significantly affect the therapeutic effect of lower extremity ASO.