Optical coherence tomography (OCT) is a fiber-optic technology that enables high-resolution intracoronary imaging. The aim of this study was to evaluate the safety and feasibility of intracoronary imaging with OCT in the clinical setting; 76 patients with coronary artery disease from 8 centers were enrolled. The OCT imaging system (ImageWire, Light Imaging Inc., Westford, Massachusetts) consists of a 0.006 inch fiber-optic core that rotates within a 0.016 inch transparent sheath. OCT imaging was performed during occlusion of the artery with a compliant balloon and continuous flushing. Intravascular ultrasound (IVUS) imaging was performed in the same segments. We assessed the safety and feasibility of the OCT imaging, compared with IVUS. Vessel occlusion time was 48.3 +/- 13.5 seconds and occlusion-balloon pressure was 0.4 +/- 0.1 atmospheres. Flushing with lactated Ringer's solution was performed at a rate of 0.6 +/- 0.4 ml/s. No significant adverse events, including vessel dissection or fatal arrhythmia, were observed. Procedural success rates were 97.3% by OCT and 94.5% by IVUS. The OCT image wire was able to cross 5 of 6 tight lesions that the IVUS catheter was unable to cross. Of the 98 lesions in which both OCT and IVUS were successfully performed, OCT imaging had an advantage over IVUS for visualization of the lumen border. Minimum lumen diameter and area measurements were significantly correlated between OCT and IVUS imaging (r = 0.91, p <0.0001 and r = 0.95, p <0.0001, respectively). In conclusion, this multicenter study demonstrates the safety and feasibility of OCT imaging in the clinical setting.