Objective To study the feasibility of using fractional flow reserve (FFR) to guide whether to perform coronary revascularization of non-culprit moderate stenosis in patients with unstable angina and estimate their clinical prognosis. Methods This study enrolled unstable angina patients with multivessel disease. First successful stenting of the culprit artery, then the other non-culprit moderate coronary stenosis were randomized into PCI guided by angiography or guided by FFR measurements. Death from any cause, nonfatal myocardial infarction, unplanned hospitalization leading to urgent revascularization and clinical manifestations with angina were followed during the first year. Results 71 patients were included, among them 35 patiens were randomly assigned to angiography-guided PCI and 36 patients to FFR-guided PCI. In FFR-guided PCI group, FFR was successfully measured in all of non-culprit moderate coronary stenosis. In 23 stenosis, the FFR was greater than 0.80, and stents were not placed in these stenosis. In 13 stenosis with FFR<0.8, stent were inplant and FFR was raised≥0.95 after stenting. The percentage of patients who had a primary end-point event was higher in the angiography-guided PCI group than the FFR-guided PCI group (P<0.05). Neither the rate of mortelity from any cause nor the rate of non-fatal myocardial infarction had significant difference between the 2 groups. Related to the target vessels rates of nonfatal myocardial infarction (5.6%vs. 28.6%) and target lesion revascularization (5.6%vs. 31.4%) were statistically different (P<0.01 and P<0.05, respectively). Conclusions In patients with unstable angina, it is safe to use FFR values to guide decisions on the revascularization of angiographically moderate non-culprit stenosis. Routine measurement of FFR in addition to angiographic guidance, as compared with PCI guided by angiography alone, results in a significant reduction in major adverse events at 1 year, particularly in urgent revascularization, and clinical manifestations with angina get better.