Background: Coronary angiography (CAG) and fractional flow reserve (FFR) are currently used to identify the lesions and guide the treatment of unstable angina (UA) patients. This study aims to compare the two methods and investigate factors affecting FFR value. Methods: A total of 284 UA patients (296 coronary artery lesions) were enrolled from the Emergency Department of Anzhen Hospital Affiliated to Capital Medical University from January 2017 to December 2017. CAG and FFR determination were performed in all patients, and the roles of these two methods in guiding the treatment of UA were compared and analyzed. The subjects were divided into FFR <= 0.8 group and FFR >0.8 group. The general data and laboratory findings were compared between these two groups, and the possible influential factors were analyzed. The statistical analysis of t-test or chi square test was done with SPSS 20.0 software. Results: Of 296 UA lesions, 160 (54.1%) had >= 75% angiographic stenosis and 136 (45.9%) had <75% angiographic stenosis; 168 (56.8%) had an FFR value of <= 0.8 and 128 (43.2%) had an FFR value >0.8. There was no significant difference between these two examination methods (P=0.508, chi(2)=0.438). Further analysis showed that 43 (26.9%) of the 160 lesions with >= 75% stenosis had an FFR value of >0.8 and did not require PCI; 49 (38.3%) of the 128 lesions with 50-70% stenosis had an FFR value of 50.8 and needed PCI; 2 of 8 patients with <50% stenosis had an FFR value of <= 0.8 and needed PCI. If FFR was used as the "gold standard" of PCI, the sensitivity, specificity, positive predictive value, and negative predictive value of CAG in guiding PCI for UA were 69.6%, 66.4%, 73.1%, and 62.5%, respectively. Multivariate analysis with Logistic regression revealed low high-density lipoprotein (HDL) and hypertension were independent risk factors of FFR <0.8 in UA patients. Conclusions: CAG and FFR readings could be different. A combination of CAG and FFR may help to achieve more accurate and tailored treatment of UA. The history of hypertension is an independent risk factor for FFR in UA patients, and HDL is an independent protective factor.