Aim To explore the predictive value of serum osteopontin （OPN） level on in-stent restenosis （ISR） after percutaneous coronary intervention （PCI）. Methods A total of 120 patients（68 males and 52 females） with acute coronary syndrome or stable angina pectoris successfully treated with PCI were collected,who were followed-up for 1 year and reexamined with coronary angiography （CAG）. The average age of the patients was 59.38±11.13. According to the results of CAG,study subjects were divided into ISR group and non-ISR group. Clinical data,serum OPN and other biochemical patameters were analyzed and compared between two groups. Results The level of serum OPN was significantly higher in ISR group than that in non-ISR group （4.79±1.09 μg/L vs 3.11±1.13 μg/L,P<0.01）. Multivariate Logistic regression analysis revealed that high serum OPN was an independent risk factor of ISR （OR＝3.034,95%CI: 1.532～6.007,P<0.01）. Area under the receiver operating characteristic curve （ROC） for OPN in evaluating prognosis of ISR patients was 0.872 （95%CI: 0.770～0.975,P<0.01）. The optimal cut-off value of OPN was 4.16 μg/L,at that point,the positive predictive rate for ISR was 56.5%,negative rate was 95.9%,sensitivity was 76.5%,specificity was 89.3%,and accuracy was 88.3%. Conclusions Serum OPN level is closely related with ISR after PCI. It has a certain predictive value for the occurrence of ISR,and its negative rate is especially high.