Background: Fractional flow reserve (FFR) is a “golden standard” in determining hemodynamic significance of ambiguous lesions and provides guidance on appropriateness of revascularization. The cut-off values for intravascular ultrasound (IVUS) parameters corresponding to FFR of 0.75 or 0.80 are still under investigation. The aim of this study was to determine best IVUS criteria for predicting physiological significance of left main coronary artery (LMCA) stenosis with FFR as the standard. Methods: FFR values during adenosine infusion (at the rate of 140 g/kg/min femoral vein) were calculated in 99 patients aged 58 10 years with an angiographically ambiguous LMCA stenosis. Subsequently, all patients underwent IVUS with automatic pullback at a constant speed of 0.5 mm/sec., from the middle segment of left descending artery (LAD) to the aorto-ostial junction of LMCA. The following IVUS parameters were analyzed: minimum lumen area (MLA, mm), minimum lumen diameter (MLD, mm), the maximum plaque burden (PB, %), and percent area stenosis (%AS, %). Results: The averaged FFR was 0.77 0.10 (range 0.51-0.99). FFR 0.75 was observed in 42 patients (42.4%). Linear regression analysis revealed a strong correlation between the values of FFR and MLA (AUC 0.86, p 0.001), PB (AUC 0.64, p 0.03), %AS (AUC 0.72, p 0.0002) and the MLD (AUC 0.75, p 0.0001). Cut off points for the value of FFR 0.75 were: 5.9 mm for MLA (sensitivity 0.69 and specificity 0.85), 59.7% for PB (sensitivity 0.77 and specificity 0.48), 36% for %AS (sensitivity 0.94 and specificity 0.44) and 2.9 mm for MLD (sensitivity 0.97 and specificity 0.50), respectively. Conclusions: Strong correlation between FFR and LMCA lesion critical IVUS parameters was found in our patient group. MLA value of 5.9 mm in IVUS seems to be a useful criterion for predicting FFR 0.75.