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The present study aimed to prospectively evaluate whether application of the concept of fractional flow reserve (FFR) guides the immediate decision to perform or to defer coronary angioplasty in unselected consecutive patients with one or more angiographically intermediate (50–70%) stenoses and non-conclusive or lacking non-invasive testing.We studied 112 patients (81 males and 31 females, aged 31–81 years) including 71 multivessel disease patients (63%) and 30 patients (27%) with unstable symptoms. FFR was measured with the use of a pressure-wire after adenosine-induced hyperaemia and compared with quantitative coronary angiography in 171 stenoses. Coronary angioplasty was performed in the presence of an FFR < 0.75 and deferred if FFR was ≥ 0.75. Cardiac events including death, myocardial infarction, recurrent angina or symptoms requiring repeated hospitalization and target vessel revascularization (TVR) were recorded during a median period of 34 months (interquartile range 9–54 months).Coronary angioplasty was deferred based on FFR results in 54 patients (group I). In the remaining 58 patients, angioplasty was performed in one or more stenoses that were significant by FFR and deferred in non-significant stenoses (group II). Overall, coronary angioplasty was performed in 71 vessels (41%) and deferred in 100 (59%). Cumulative cardiac events occurred in 12.9% of group I patients and in 24.1% of group II patients (χ2 = 1.57, P = 0.20). TVR was required in 5% of the stenoses untreated based on FFR result in both groups and in 12.6% of stenoses that underwent coronary angioplasty (χ2 = 3.25, P = 0.07; relative risk = 2.5, 95% confidence interval = 0.88–8.61).In patients with angiographically intermediate stenoses, functional evaluation by FFR to select lesions that do not need to be treated invasively is safe. Unnecessary angioplasty and stenting may be saved in more than one half of individual coronary stenoses. The risk of major cardiac events and TVR of functionally non-significant stenoses is lower than the risk associated with coronary angioplasty. Our observations further support the use of pressure wire for physiological assessment of coronary artery stenosis in the catheterization room.