Objective To explore the clinical effect and possible mechanism of tirofiban combined with double antibodies in the treatment of progressive stroke. Methods A total of 116 patients with progressive stroke were randomly divided into control group and observation group, 58 patients in each group. The patients in the control group were treated with double antithrombotic therapies (aspirin combined with clopidogrel) alone. Patients in the observation group were treated sequentially with tirofiban combined with double antithrombotic therapies. After the treatment, the degree of neurological impairment, daily living ability and neurological function recovery of the two groups were observed and compared; serum hs-crp level and coagulation function were monitored, and clinical efficacy was evaluated and adverse reactions were recorded. Results Compared with patients before treatment, the scores of 14th d, 30th d and 90th d NIHSS in the two groups after treatment were decreased, while the scores of BI were increased, and the mRS scores of 90d after treatment were decreased. At 14d, 30d and 90d after treatment, the NIHSS score of the observation group was lower than that of the control group, the BI score was higher than that of the control group, and the mRS score of 90d after treatment was lower than that of the control group, the differences were statistically significant (P < 0.05). The levels of hs-crp, fibrinogen and d-dimer in the observation group were all lower than those in the control group 14 days after treatment, and the difference was statistically significant (P < 0.05). The total effective rate in the observation group (94.83%) was higher than that in the control group (77.59%), and the difference was statistically significant (P < 0.05). No serious adverse reactions occurred during the treatment in the two groups. Conclusions In the treatment of patients with progressive stroke, tirofiban combined with double antithrombotic therapies can significantly reduce platelet accumulation and thrombolysis, and have significant effects in improving the symptoms of neurological defects and improving the quality of daily life, as well as alleviating vascular inflammatory reaction and improving blood coagulation function, which is worthy of clinical promotion.