The active surveillance of root caries lesions to monitor potential remineralization or decay progression is challenging for the clinician, due to unreliable diagnostic information. The conventional visual and tactile methods for assessing the lesion activity are not reliable, and the clinician is often unable to determine if the lesion is progressing or has been arrested. An important marker of an arrested lesion is a highly mineralized transparent surface zone (TSL) that forms when the mineral is deposited in the outer layer of the lesion. The purpose of this study was to determine if cross-polarization optical coherence tomography (CP-OCT) could be used to detect changes in the lesion severity and activity during active monitoring. In total, 18 subjects with 22 suspected active root caries lesions were evaluated using CP-OCT at the baseline, 3 months, and 6 months. All subjects were instructed to use a high fluoride dentifrice at the baseline. The results showed that CP-OCT was able to discriminate the active from the arrested lesions by identifying the presence of a TSL on arrested lesions. The results also indicated that the mean TSL thickness increased significantly (p < 0.05) for the nine lesion areas. In addition, CP-OCT was able to show the progression of demineralization, erosion, and changes in gingival contours in scanned areas. CP-OCT was valuable for monitoring the activity and severity of root caries lesions in vivo. CP-OCT can be used to assess the activity of root caries lesions at a single time point by detecting the presence of a TSL at the lesion surface indicative of the lesion arrest.