Dental enamel mineral loss is multifactorial and is consequently explored using a variety of in vitro models. Important factors include the presence of acidic pH and its specific ionic composition, which can both influence lesion characteristics. Optical coherence tomography (OCT) has been demonstrated as a promising tool for studying dental enamel demineralization. However, OCT-based characterization and comparison of demineralization model dynamics are challenging without a consistent experimental environment. Therefore, an automated four-dimensional OCT system was integrated with a multispecimen flow cell to measure and compare the optical properties of subsurface enamel demineralization in different models. This configuration was entirely automated, thus mitigating any need to disturb the specimens and ensuring spatial registration of OCT image volumes at multiple time points. Twelve bovine enamel disks were divided equally among three model groups. The model demineralization solutions were citric acid (pH 3.8), acetic acid (pH 4.0), and acetic acid with added calcium and phosphate (pH 4.4). Bovine specimens were exposed to the solution continuously for 48 h. Three-dimensional OCT data were obtained automatically from each specimen at a minimum of 1-h intervals from the same location within each specimen. Lesion dynamics were measured in terms of the depth below the surface to which the lesion extended and the attenuation coefficient. The net loss of surface enamel was also measured for comparison. Similarities between the dynamics of each model were observed, although there were also distinct characteristic differences. Notably, the attenuation coefficients showed a systematic offset and temporal shift with respect to the different models. Furthermore, the lesion depth curves displayed a discontinuous increase several hours after the initial acid challenge. This work demonstrated the capability of OCT to distinguish between different enamel demineralization models by making dynamic quantitative measurements of lesion properties. This has important implications for future applications in clinical dentistry. © The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI.