We assessed the long-term (>10 years) clinical course of patients with documented coronary lesions deemed nonsignificant according to fractional flow reserve (FFR) assessment and investigated whether the initial FFR value impacted on prognosis. From January 2000 to October 2003, all patients submitted to coronary angiography with FFR measurement were included in a single-center, prospective registry. Patients with an FFR value >0.80 were treated medically without revascularization. Major adverse cardiac events (MACE) (death, acute coronary syndrome (ACS), or coronary revascularization) were compared according to initial FFR value (absolute value and by category, ≤0.90 vs >0.90). Analyses were performed using a multivariable Cox model and propensity score matching. Among 257 patients (332 lesions) treated medically initially, 131 (51%, 143 lesions) had FFR ≤0.90 and 126 (49%, 189 lesions) >0.90. During follow-up (median duration, 11.6 years), 82 (31.9%) had a MACE, 38 (14.8%) died, 17 (6.6%) had ACS, 93 (36.2%) had repeat coronary angiography, and 27 (10.5%) had revascularization. There was no clinical, biologic or angiographic difference between patients with initial FFR value ≤0.90 versus >0.90. Adjusted Cox model showed no difference in relative risk of MACE, death, ACS, or revascularization. Coronary angiographies were numerically more frequent in patients with FFR ≤0.90, versus FFR >0.90. These findings were confirmed by propensity score–matched comparison. In patients with coronary narrowings left unrevascularized based on FFR, an FFR value between 0.80 and 0.90 has no impact on long-term outcome compared with those with FFR >0.90. In conclusion, patients with high FFR values should not be considered as having a lower risk of coronary event.