Frequency domain optical coherence tomography (FD-OCT) provides cross-sectional images of coronary arteries and deployed stents with micron resolution and measures lumen dimensions with excellent reproducibility. FD-OCT combined with a blood flow resistances model can overcome many limitations of conventional measures of stenosis severity based on quantitative coronary angiography (QCA) and intravascular ultrasound (IVUS). The aim of this feasibility study was to investigate the relationship between pressure derived fractional flow reserve (FFR) and FD-OCT derived FFR, a new method for quantitative measure of stenosis severity that estimates the blood flow resistance and microvascular resistance of the vessel segments imaged by FD-OCT. A total of 26 coronary stenoses in 20 patients were studied consecutively with QCA, pressure derived FFR, and FD-OCT. There was a moderate but significant correlation between pressure derived PER and FD-OCT derived PER (r = 0.69, P < 0.001). Bland-Altman analysis showed that the mean differences between pressure derived FFR and FD-OCT derived FFR were 0.05 +/- 0.14 (limits of agreement: -0.09 to 0.19). The root mean square error (RMSE) between FD-OCT derived FFR and pressure derived FFR was found to be +/- 0.087 FFR units. FD-OCT derived FFR has the potential to become a valuable tool for the assessment of coronary artery stenosis.