Purpose Coronary flow reserve (CFR) is recognized as an indicator of myocardial perfusion. The aim of this study was to assess the relationship between CFR in the non-infarcted myocardium and the incidence of major adverse cardiac events (MACEs). Materials and Methods 100 consecutive patients with acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI) were enrolled in the present study, and divided into MACE and non-MACE groups according to the incidence of 12-month MACEs. Left ventricular function and CFR were analyzed using two-dimensional echocardiography and myocardial contrast echocardiography at one week after PCI. Cardiac troponin I levels were assayed to estimate peak concentrations thereof. Results The MACE group was associated with lower CFR, compared to the non-MACE group (2.41 vs. 2.77, p <0.001). In the multivariable model, CFR in the non-infarcted myocardium was an independent predictor of 12-month MACE (hazard ratio: 0.093, 95% confidence interval: 0.020–0.426, p =0.002) after adjustment for baseline demographic and clinical characteristics. Conclusion CFR in the non-infarcted myocardium is a useful marker for predicting 12-month MACEs in patients with AMI undergoing primary PCI.