The success rate of percutaneous transluminal coronary angioplasty for chronic total arterial occlusions is still unsatisfactory. Inability to cross the lesion with a guidewire is a major cause of failure. Optical coherent reflectometry (OCR) is a new method of using laser light to measure the depth of tissue from the end of an optic fiber. This study tests whether an OCR prototype guidewire provides a guidance system that might be useful to assist reopening chronic total arterial occlusions. An OCR fiber optic within a 0.014″ hypotube was developed using the interference pattern of two reflected light beams (wave length 1,300 nm). To determine if OCR can distinguish different tissue types, plaques of human lower extremity arterial segments were visually divided into three types (calcified, white, or yellow). The slope of the initial reflectance of the OCR curve was calculated and compared between the three groups. In six other arteries, the OCR wire was advanced longitudinally through occluded human artery segments in vitro. Guidewire position was determined by OCR and compared to the position of the guidewire tip observed simultaneously by intravascular ultrasound (IVUS) imaging. In 16 arterial surface segments, calcified plaques had a significantly steeper slope than white or yellow plaques (−227.2 ± 82.2; −81.5 ± 12.9; −103.6 ± 19.6 dB/mm; P < 0.01). For the determination of the guidewire position, IVUS and OCR corresponded correctly in 82% of 28 measurements. Sensitivity and specificity of OCR for detection of plaque versus the media/adventitia boundary were 79% and 89%, respectively (P < 0.001). OCR can distinguish calcified from noncalcified plaque and may distinguish plaque from the media/adventitia boundary. This technology may be useful as a means to help navigate a guidewire safely through an occluded artery. Cathet Cardiovasc Intervent 2001;54:257–263. © 2001 Wiley‐Liss, Inc.