Abstract: Objective To study the efficacy of clopidogrel plus aspirin in treatment of non-cardiogenic acute cerebral infarction and safety assessment. Methods A retrospective analysis was carried on for the patients with non-cardiogenic acute cerebral infarction who are unable or refusing to undergo thrombolytic therapy in the first people's hospital of Chuzhou from September 2015 to March 2017. Thirty patients were randomly selected from the patients treated with clopidogrel plus aspirin as the observation group. Thirty patients were randomly selected from the patients treated with aspirin as the control group. All of them had been given chewing aspirin 100 mg at the emergency department. The observation group oral clopidogrel 75 mg combined with aspirin 100 mg daily and the control group oral aspirin 100 mg daily from the day of admission. After 3 weeks treatment, the NIHSS score, total effective rate, the levels of plasma fibrinogen and homocysteine were compared between the two groups. The recurrence rate of cerebral infarction and the incidence of adverse drug reactions in 1-year follow-up visits between the two groups were compared. Results After 3 weeks treatment, the NIHSS score, total effective rate, the levels of plasma fibrinogen and homocysteine decrease effectively compared to the time of the admission (P<0.05). The total effective rate of observation group (93.33%) was significantly higher than that in control group (70.00%, P<0.05). During 1 year follow-up, the recurrence rate of cerebral infarction in observation group was 6.67%, significantly lower than that in control group (30.00%,P<0.05). The incidence of adverse reactions between the two groups had no significant (P>0.05) and no cerebral hemorrhage occurred in both groups. Conclusion For the treatment of non-cardiogenic acute cerebral infarction patients, comparing with aspirin alone, clopidogrel combined with aspirin can significantly improve the treatment effect of patients with acute cerebral infarction, and effectively reduce the levels of plasma fibrinogen and homocysteine in patients. It can also effectively reduce the recurrence rate of cerebral infarction, and there is no significant increase in adverse drug reactions.