This clinical study tested cross-polarization optical coherence tomography (CP-OCT) monitoring of erosive tooth wear (ETW). Twenty participants completed a 14-day/arm, 3-arm crossover study simulating different ETW severities. Participants received two enamel specimens (per arm) and were randomized to: severe (s-ETW, lemon juice/pH:2.5/4.25%wt/vol citric acid), moderate (m-ETW, grapefruit juice/pH:3.5/1.03%wt/vol citric acid), and non-ETW (water). Enamel thickness was measured with CP-OCT (day[D] 0, 7, 14) and micro-computed tomography (μ-CT; D14). Enamel surface loss was determined with CP-OCT and optical profilometry (OP; D7, D14). CP-OCT showed higher enamel surface loss for D14 than D7 for m-ETW (P = .009) and s-ETW (P = .040) and differentiated severity at D14 (s-ETW > non-ETW, P = .027). OP was able to differentiate surface loss between days (D7 < D14, P < .001) for m-ETW and s-ETW, and ETW severity effect after 7 and 14 days (non-ETW < m-ETW < s-ETW, P < .001). At D14, CP-OCT and μ-CT were positively correlated (r = .87, ICC = .62). CP-OCT showed potential as a tool for clinical ETW monitoring.