Objective To investigate the value of serum brain natriuretic peptide and high sensitivity C-reactive protein in the prognosis of acute ischemic stroke patients after 3 months. Methods 114 acute ischemic stroke patients were collected in our hospital. 52 good recovery patients and 24 poor recovery patients were randomly selected for the model building, and the remaining 26 good recovery patients and 12 poor recovery patients were used for the model validating. In the training group and validation group, the sex and age of good recovery group and poor recovery group showed no significant difference. Plasma brain natriuretic peptide and high-sensitivity C-reactive protein levels were detected in all samples, and receiver operating characteristic curve was used to evaluate their diagnostic value. Results The risk factors including smoking, drinking, high blood pressure, high blood sugar and high cholesterol showed no significant difference between the good recovery group and poor recovery group (P>0.05). There were significant difference on the brain natriuretic peptide and high-sensitivity C-reactive protein levels between the two groups (P<0.05). When combined analysis brain natriuretic peptide and high-sensitivity C-reactive protein, the area under the curve was 0.86 (0.79, 0.93), the sensitivity and specificity were 84.61% and 79.17%, separately. After validation, the diagnostic sensitivity and specificity were 80.77% and 75%, separately. Conclusion The combined detection of brain natriuretic peptide and high-sensitivity C-reactive protein may provide an effective potential method to assess the 3 months prognosis of acute ischemic stroke patients.