Objective: We aimed to assess the ideal cut-off value of minimal lumen area (MLA) by intravascular ultrasound (IVUS) and its diagnostic performance to predict ischemia, using a large-scale, pooled analysis. Methods: Eleven centers worldwide were invited to provide their clinical, IVUS and fractional flow reserve (FFR) data. A total of 881 lesions were enrolled. Results: Angiographic % diameter stenosis (r = -0.373, p < 0.0001) and IVUS MLA (r = 0.289, p < 0.0001) correlated with FFR. Best cut-off value (BCV) of IVUS MLA to define the functional significance (FFR <0.8) was 2.75 mm2 (AUC 0.646, 95% CI 0.609-0.684). When the diagnostic performance of IVUS MLA was tested according to the lesion location, BCV could be found only in lesions in the proximal artery and the mid-left anterior descending artery. Interestingly, Asians (n = 623) and Westerners (n = 258) showed different demographic and lesion characteristics as well as different BCVs to define ischemia. The BCV for the proximal/mid-left anterior descending artery lesions was 2.75 mm2 (AUC 0.688, 95% CI 0.635-0.742) in Asians and 3.0 mm2 (AUC 0.695, 95% CI 0.605-0.786) in Westerners. Conclusion: In this pooled analysis, an IVUS MLA of 2.75 mm2 was the BCV to define the functional significance of intermediate coronary stenosis. However, when IVUS MLA is used to determine the functional significance, both the lesion and patient characteristics should be considered.

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