Optical coherence tomography (OCT) is a recently developed technology which can perform micron scale, cross sectional tomographic imaging. OCT performs imaging using interferometric optical ranging of low coherence infrared light or ultrashort laser pulses which are backscattered from tissue. This technique is analogous to the reflected acoustical wave measurements of conventional B mode ultrasound. In this study, two dimensional cross sectional images were generated of in vitro human aorta and coronary artery sections obtained postmortem. The microstructure of normal and atherosclerotic tissue was displayed as a false color or grey scale image. The bandwidth of the photodiode source (1300 nm) allowed a resolution of 20 microns, almost 10 times greater than conventional intravascular ultrasound. Different morphologies including fatty, fibrous, and water based tissue, were well differentiated in the images and corresponded to histologic sections. Imaging was possible with up to 1 mm penetration into the tissue with little attenuation from heavy calcification. The typical image acquisition time was in the range of 2–3 seconds. A more detailed analysis of the optical properties of relatively uniform, structurally distinct tissues, such as adipose, skeletal muscle, and tendon, was performed to further confirm the contrast between fat, muscle, and connective tissue. The contrast ratios of muscle, tendon, and fat, were measured to be 1:78:22, respectively. The effective refractive indices and optical penetration depths in different tissue types were also measured. OCT is a promising new technology for high resolution “optical biopsy”. It does not require direct contact with the vessel wall and could be performed via a catheter integrated with a relatively inexpensive fiberoptic bundle. Future studies utilizing currently available femtosecond lasers are expected to both increase the resolution of OCT, which is dependent on bandwidth or pulse duration. to ≈3–4 microns and allow visualization of structures deeper into tissues.