Objectives: To characterize the cariostatic potential of a low-energy Er:YAG laser treatment. Methods: Twelve sound premolars were selected. Two 2 × 1 mm windows were created on each tooth and randomly assigned to L1 and L2 groups. Three sites in each window were chosen with the middle site as the control and the left and right ones receiving Er:YAG laser treatment of 5.1 J/cm2 (L1) or 2.0 J/cm2 (L2), respectively. The teeth were further subjected to 4-day pH cycling to create caries-like lesions. After mineral quantification using a micro-computed tomography scanner, the preventive effects (ΔML = mineral loss of the control area minus that of the lased area) of L1 and L2 treatments were calculated based on the difference in the gray value of the control and lased sites. Results: Significant inhibitory effects of L1 and L2 on enamel demineralization were demonstrated (both p ≤ 0.001), with the L1 treatment having a greater effect (45.2%) than the L2 treatment (25.2%, p = 0.004). Conclusions: Subablative low-energy Er:YAG laser irradiation can significantly prevent enamel demineralization potentially through the retardation of enamel diffusion. This study confirmed that high-energy laser treatment, which may damage the peripheral and underlying tissues, may not be needed for caries prevention.

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