This study sought to evaluate the long-term clinical outcome of patients with an angiographically intermediate left anterior descending coronary artery (LAD) stenosis in whom the revascularization strategy was based on fractional flow reserve (FFR).When revascularization is based mainly on angiographic guidance, a number of hemodynamically nonsignificant stenoses will be revascularized.In 730 patients with a 30% to 70% isolated stenosis in the proximal LAD and no significant valvular disease, FFR measurements were obtained to guide treatment strategy. When FFR was ≥0.80, the patients (n = 564) were treated medically (medical group); when FFR was <0.80, the patients (n = 166) underwent a revascularization procedure (revascularization group; 13% coronary artery bypass graft surgery and 87% percutaneous coronary intervention). A 100% long-term clinical follow-up (median follow-up: 40 months) was obtained. The 5-year survival of the medical group was compared with that of a reference population. For each patient, 4 controls were selected from an age- and sex-matched control population.The 5-year survival estimate was 92.9% in the medical group versus 89.6% in the controls (p = 0.74). The mean diameter stenosis was significantly smaller in the medical than in the revascularization group (39 ± 14% vs. 54 ± 13%, p < 0.0001), but there was a large overlap between both groups. The 5-year event-free survival estimates (death, myocardial infarction, and target vessel revascularization) were 89.7% and 68.5%, respectively (p < 0.0001).Medical treatment of patients with a hemodynamically nonsignificant stenosis (FFR ≥0.80) in the proximal LAD is associated with an excellent long-term clinical outcome with survival at 5 years similar to an age- and sex-matched control population.