Background: A large, prospective, multicentre trial recently showed that fractional flow reserve (FFR) derived from coronary angiography (FFR_angio) has an accuracy of 92% compared with conventional guidewire-based FFR (FFR_wire); however, little is known about whether specific patient/lesion characteristics affect the diagnostic performance. Aims: The primary goal of the present study was to investigate whether specific patient or lesion characteristics such as high body mass index (BMI), presentation with an acute coronary syndrome, or lesion location affect the diagnostic performance of FFR_angio in patients enrolled in the FAST-FFR study. Methods: FFR_angio was measured in a blinded fashion in 301 patients (319 vessels) who were undergoing FFR_wire assessment. Using an FFR_wire ≤0.80 as a reference, the diagnostic performance of FFR_angio was compared in pre-specified subgroups. Results: The mean FFR_wire and FFR_angio were 0.81±0.13 and 0.80±0.12. Overall, FFR_angio had a sensitivity of 93.5% and specificity of 91.2% for predicting FFR_wire. Patient characteristics including age, sex, clinical presentation, body mass index, and diabetes did not affect sensitivity or specificity (p>0.05 for all). Similarly, lesion characteristics including calcification and tortuosity did not affect sensitivity or specificity (p>0.05 for all), nor did lesion location (proximal, middle, versus distal). Sensitivity was equally high across all target vessels, while specificity was highest in the LAD and lower (~85%) in the RCA and LCx (p<0.05). Conclusions: FFR_angio derived from coronary angiography has a high diagnostic performance regardless of patient and most lesion characteristics. The interaction of vessel on the specificity will need to be confirmed in larger cohorts.