We present an animal study to examine the utility and potential limitations of optical coherence tomography (OCT) for noninvasive evaluation of biomaterial scaffold-assisted wound healing. The transverse and axial resolutions of the OCT system at the wavelength of 1.3 microm were 12 and 10 microm, respectively. A murine full-thickness transcutaneous wound model was employed, in which a phi 10 mm full-thickness wound was created on the back of each male Balb/cJ mouse and a porous collagen scaffold was implanted in the wound bed followed by coverage with a Tegaderm film. Sequential cross-sectional OCT scans were performed at different time points postsurgical intervention to track morphological changes during wound recovery, and the captured OCT images were validated by their corresponding histological specimens. The results indicated that with removal of the high-scattering skin, OCT was capable of imaging to a depth of over 1.5 mm into the wound bed and differentiating various features evolved during wound healing at a high resolution approaching histopathology. OCT was able to not only delineate the epidermis and dermis of normal mouse skin, but also differentiate collagen implant from the underlying subcutaneous tissue; besides, it could track the wound size changes in both lateral and vertical directions. More importantly, OCT was able to detect inflammation, early re-epithelialization, and resorption of the collagen scaffold. These findings suggested the potential of OCT for noninvasive and high-resolution monitoring of assisted wound healing in vivo, longitudinally, and instantaneously.