Studies have shown that lasers can be used to modify the chemical composition of tooth enamel to render it less soluble. The purpose of this study was to determine if polarization-sensitive optical coherence tomography (PS-OCT) can be used to nondestructively assess the inhibition of demineralization after CO2 laser irradiation. Human and bovine enamel specimens were irradiated by a microsecond pulsed CO2 laser operating at a wavelength of 9.3 microm. Some specimen areas were also treated with topical fluoride to create six treatment groups on each sample, including protected surface (no demineralization), protected +laser, laser, fluoride, laser+fluoride, and unprotected surface. Samples were placed in an artificial demineralization solution to create lesions approximately 100-200 microm in depth and were subsequently scanned with a PS-OCT system to assess lesion severity before sectioning for analysis by polarized light microscopy and transverse microradiography for comparison. PS-OCT was able to measure a significant reduction in the integrated reflectivity due to inhibition by the laser on both human and bovine enamel even though the laser modification of the enamel surface did cause an increase in reflectivity and decrease in optical penetration. This study shows that the PS-OCT is well suited for the clinical assessment of caries inhibition after laser treatments.