Background - Intravascular ultrasound (IVUS) is being used to assess the significance of a left main coronary artery stenosis (LMCS). However, the cutoff values of IVUS parameters at which to predict a fractional flow reserve (FFR) of 0.75 are unknown. Methods and Results - In 55 patients with an angiographically ambiguous LMCS, a pressure guidewire was used to calculate FFR, and IVUS parameters were calculated after automatic pullback. FFR averaged 0.86±0.13 (range, 0.55 to 1.0). IVUS minimum lumen diameter (MLD), minimum lumen area (MLA), cross-sectional narrowing (CSN), and area stenosis (AS) were 3.8±0.61 mm, 7.65±2.9 mm2, 59±13%, and 47±19%, respectively. Regression analysis demonstrated strong correlations between FFR and MLD (r=0.79, P<0.0001) as well as between FFR and MLA (r=0.74, P<0.0001). There were inverse, moderate correlations between FFR and CSN (r=0.69, P<0.0001), followed by those between FFR and AS (r=0.54, P<0.0001). Compared with FFR as the "gold standard," an MLD of 2.8 mm had the highest sensitivity and specificity (93% and 98%, respectively) for determining the significance of an LMCS, followed by an MLA of 5.9 mm2 (93% and 95%, respectively). Based on an FFR <0.75 and an FFR ≥0.75, the 38-month survival and event-free survival estimates (EFSEs) were both 100% and 100% versus 90%, respectively (P=NS). Conclusions - We conclude that (1) an IVUS MLD and MLA of 2.8 mm and 5.9 mm2, respectively, strongly predict the physiological significance of an LMCS and (2) among patients with an LMCS, an FFR of 0.75 is a strong predictor of survival and EFSE.