Fractional flow reserve (FFR) and intravascular imaging respectively provide hemodynamic and anatomical assessments of angiographic intermediate stenoses. Frequency domain optical coherence tomography (FD-OCT) is a promising high-resolution imaging modality, but its clinical use in determining severity of coronary disease has yet to be determined. There, we set out to determine the role of FD-OCT to complement FFR in the evaluation of intermediate coronary artery stenoses. FD-OCT was planned in 176 consecutive interventional procedures at our institution to delineate the proper use of FD-OCT in clinical practice. The decision to use other invasive assessments was at the discretion of the operator. This report describes an early series of the 14 patients who underwent FFR of 18 target stenoses in addition to FD-OCT. FD-OCT was successfully performed without complications in all cases. Fractional flow reserve was <0.80 in four patients, with minimal lumen areas and reference vessel diameters ranging from 1.03 to 3.47 mm(2) and 2.60 to 2.94 mm by FD-OCT, respectively. FD-OCT was important to rule out plaque rupture, erosion and thrombosis and to help guide decision to defer PCI in six patients with acute coronary syndrome and FFR > 0.80. FD-OCT was also valuable to guide PCI strategy in tandem lesions with an FFR < 0.80. This initial experience with FD-OCT suggests a potential complementary role of physiological and anatomical assessment to guide decision making in complex clinical scenarios. Future investigations are warranted to validate these findings and define the role of FD-OCT in assessing intermediate lesions.