Background Global fractional flow reserve (FFR) (ie, the sum of the FFR values in the 3 major coronary arteries) is a physiologic correlate of global atherosclerotic burden. The objective of the present study was to investigate the value of global FFR in predicting long‐term clinical outcome of patients with stable coronary artery disease but no ischemia‐inducing stenosis. Methods and Results We studied major adverse cardiovascular events (MACEs: all‐cause death, myocardial infarction, and any revascularization) after 5 years in 1122 patients without significant stenosis (all FFR >0.80; n=275) or with at least 1 significant stenosis successfully treated by percutaneous coronary intervention (ie, post–percutaneous coronary intervention FFR >0.80; n=847). The patients were stratified into low, mid, or high tertiles of global FFR (≤2.80, 2.80–2.88, and ≥2.88). Patients in the lowest tertile of global FFR showed the highest 5‐year MACE rate compared with those in the mid or high tertile of global FFR (27.5% versus 22.0% and 20.9%, respectively; log‐rank P =0.040). The higher 5‐year MACE rate was mainly driven by a higher rate of revascularization in the low global FFR group (16.4% versus 11.3% and 11.8%, respectively; log‐rank P =0.038). In a multivariable model, an increase in global FFR of 0.1 unit was associated with a significant reduction in the rates of MACE (hazard ratio [HR], 0.988; 95% CI, 0.977–0.998; P =0.023), myocardial infarction (HR, 0.982; 95% CI, 0.966–0.998; P =0.032), and revascularization (HR, 0.985; 95% CI, 0.972–0.999; P =0.040). Conclusions Even in the absence of ischemia‐producing stenoses, patients with a low global FFR, physiologic correlate of global atherosclerotic burden, present a higher risk of MACE at 5‐year follow‐up.