Objectives To identify clinical, angiographic and hemodynamic predictors of discordance between instantaneous wave‐free ratio (iFR) and fractional flow reserve (FFR). Background The iFR was found to be non‐inferior to the gold‐standard FFR for guiding coronary revascularization, although it is discordant with FFR in 20% of cases. A better understanding of the causes of discordance may enhance application of these indices. Methods Both FFR and iFR were measured in the prospective multicenter CONTRAST study. Clinical, angiographic and hemodynamic variables were compared between patients with concordant values of FFR and iFR (cutoff ≤0.80 and ≤0.89, respectively). Results Out of the 587 patients included, in 466 patients (79.4%) FFR and iFR agreed: both negative, n = 244 (41.6%), or positive, n = 222 (37.8%). Compared with FFR, iFR was negative discordant (FFR+/iFR‐) in 69 (11.8%) patients and positive discordant (FFR‐/iFR+) in 52 (8.9%) patients. On multivariate regression, stenosis location (left main or proximal left anterior descending) (OR: 3.301.68;6.47), more severe stenosis (OR: 1.771.35;2.30), younger age (OR: 0.930.90;0.97), and slower heart rate (OR: 0.590.42;0.75) were predictors of a negative discordant iFR. Absence of a beta‐blocker (OR: 0.410.22;0.78), older age (OR: 1.041.00;1.07), and less severe stenosis (OR: 0.690.53;0.89) were predictors of a positive discordant iFR. Conclusions During iFR acquisition, stenosis location, stenosis degree, heart rate, age and use of beta blockers influence concordance with FFR and should be taken into account when interpreting iFR. Condensed iFR‐guided revascularization is non‐inferior to FFR at 1 year, despite being discordant with FFR in 20% of cases. In 587 patients, we studied predictive factors for this discordance. Stenosis location involving the left main or proximal left anterior descending coronary, more severe stenosis, younger age and slower heart rate were significant predictors of a negative discordant iFR (FFR+/iFR‐). Lack of use of a beta‐blocker, older age, and less severe stenosis were significant predictors of a positive discordant iFR (FFR‐/iFR+). Clinical, angiographic and hemodynamic conditions during iFR acquisition influence concordance with FFR and must be taken into account when interpreting iFR.