To investigate the effects of nimodipine and aspirin on serum S100 protein (S100), neuron-specific enolase (NSE), and C reactive protein (CRP) in patients with acute ischemic cerebral infarction as well as its effect in secondary prevention. Methods: One hundred and fifty-two patients with acute ischemic cerebral infarction were divided into the aspirin group and the combination treatment group according to their different treatment procedures. Serum levels of S100, NSE, and CRP were compared between the two groups before and after treatment, and secondary prevention conferred by the treatment methods was also compared. Results: The difference in serum levels of S100 between the two groups at 7 days and 15 days after treatment was statistically significant. The serum levels of S100, NSE, and CRP in the combination therapy group were significantly lower than those in the aspirin group (P<0.05). The proportion of patients with recurrent cerebral infarction complicated with myocardial infarction and deep vein thrombosis (DVT) in the combined treatment group was significantly lower than that in the aspirin group (P<0.05). However, the mortality rate of the patients in the combination group was not significantly different from that of the aspirin group (P>0.05). Conclusion: Nimodipine combined with aspirin can effectively reduce serum levels of S100, NSE, and CRP in patients with acute ischemic cerebral infarction and can also reduce the recurrence rate of cerebral infarction, myocardial infarction, and DVT