Aim To discuss the correlation between substance P precursor (Pro-SP) and platelet activation, platelet parameters. Methods A total of 76 patients were enrolled in the department of cardiology. According to the diagnostic criteria of acute myocardial infarction, the patients were divided into non-acute myocardial infarction group (n=39) and acute myocardial infarction group (n=38). Percentage of platelet-mononuclear aggregate (PMA) formation was evaluated for platelet activation by flow cytometry. The concentration of Pro-SP was determined by ELISA. The correlations of Pro-SP, PMA and the parameters of platelets were statistically compared, as well as the differences between the two groups in Pro-SP. Results Pro-SP was positively correlated with PMA (Pearson correlation coefficient 0.407, P<0.001) and platelet distribution width (Pearson correlation coefficient 0.269, P=0.018), but not with total platelet count, mean platelet volume, platelet specific volume, and large platelet ratio (P>0.05). Linear regression analysis showed that Pro-SP was an independent influencing factor of PMA, and Pro-SP was significantly higher in the acute myocardial infarction group than that in the non-acute myocardial infarction group (P<0.05). Conclusion Pro-SP is positively correlated with platelet activation and platelet distribution width, but not with total platelet count, average platelet volume, platelet specific volume, and large platelet ratio (P>0.05).