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To investigate the relationship between classic SYNTAX and functional SYNTAX score guided by fractional flow reserve (FFR).SYNTAX score predicts clinical outcome after percutaneous coronary intervention in patients with multivessel coronary artery disease (CAD), based on data from angiography alone. However, in the clinical setting, decision-making on myocardial revascularization should be guided by reliable demonstration of inducible ischemia, as detected by FFR.FFR was collected in all 50–90% angiographic stenoses of 39 consecutive patients with stable multivessel CAD. SYNTAX score was calculated as usually described in SYNTAX group's reports. A functional SYNTAX (F-SYNTAX) score was determined by only considering ischemia-producing lesions (FFR ≤ 0.80). The two scores were compared with correlation, Bland–Altman and agreement tests.FFR was measured in 97 lesions, with a median value of 0.82 ± 0.10. In the 50–70% and 70–90% category stenoses, FFR was greater than 0.80 in 68 and 16% of cases, respectively. F-SYNTAX was systematically inferior to SYNTAX score, with a median difference of 8.4 ± 7.4 (P < 0.05). The correlation between the two methods was globally weak (r = 0.621, rho = 0.563; P < 0.001). After determining F-SYNTAX score, more than 30% of the patients moved to a lower-risk tertile group (P = 0.003). No clinical and angiographic differences were found between patients whether or not reclassified in lower-risk tertiles with F-SYNTAX score.In patients with multivessel CAD, implementation of SYNTAX score with FFR seems to be a more rational approach for revascularization. F-SYNTAX score reclassifies a significant proportion of patients to a lower-risk profile, thus leading to a possible change of therapeutic strategy.