Aims: The objective of this study is to evaluate the feasibility and safety of imaging human coronary arteries in vivo by optical frequency domain imaging (OFDI) in comparison to intravascular ultrasound (IVUS). OFDI has been recently developed to overcome the limitations of conventional time-domain optical coherence tomography (OCT), namely the need for proximal balloon occlusion. The Terumo-OFDI system is capable of acquiring images with high-speed automated pullback (up to 40 mm/sec) and requires only a short injection (3-4 sec) of small amount of x-ray contrast (9-16 ml). Methods and results: Nineteen patients who underwent stent implantation were enrolled. IVUS/OFDI were performed before and after stenting. The incidences of any adverse event and angiographic adverse findings were recorded. Lumen area (LA) was measured by IVUS and OFDI at 1 mm intervals in the stented segments (n=19) as well as in the proximal, distal, and to-be-stented segments (n=40). In addition, lumen area in the stented segment was also measured by edge (E-) and video-densitometric (VD-) quantitative coronary angiography (QCA). The OFDI images were obtained without any adverse event related to imaging procedures. Post stenting (n=19), minimal LA (MLA) measured by OFDI (5.84±1.89 mm2) was larger than that of E-QCA (4.16±1.46 mm2, p<0.001) and VD-QCA (4.92±1.55 mm2, p<0.05). It was smaller than IVUS-MLA (6.26±2.01 mm2, N.S.) but the correlation between the two measurements was highly significant (R2=0.82, p<0.001). Conclusions: The OFDI imaging is feasible both before and after stenting and has a promising safety profile. The OFDI provided clear high resolution images and robust lumen measurements.