Nd:YAG laser-induced modification of the root surface may inhibit development of external inflammatory resorption in replanted teeth. This study tested this hypothesis in vivo. The pulp chambers of six mandibular premolars in each of two dogs were accessed, inoculated with plaque, and sealed (Groups 1, 2). Two additional premolars in each dog were endodontically treated without inoculation (Groups 3, 4). After 2 weeks, teeth were hemisected and extracted. Each root had a 2 x 3 mm surface area denuded of cementum on the buccal and lingual surface. In Groups 1 (n = 12 roots) and 3 (n = 4), the denuded surfaces were wiped with 15% EDTA, coated with black ink, and irradiated with Nd:YAG laser (0.75 W, 15 pps, 300 microns tip, 20 s). In Groups 2 (n = 12) and 4 (n = 4), the surfaces were wiped with 15% EDTA, and rinsed with sterile saline for 20 s. Roots were replanted within 5 min. The dogs were perfusion-euthanised 10 weeks after replantation. Block specimens were removed, decalcified, embedded and horizontally sectioned (6 microns) at 180-microns intervals, resulting in 10 to 14 cross-sections of each root. From these, the middle five consecutive sections were stained with hematoxylin and eosin, and observed by light microscopy for occurrence of surface, inflammatory and replacement resorption on the denuded surfaces. No obvious differences were noted between the laser-irradiated and non-irradiated surfaces. Inflammatory resorption was frequent in Groups 1 and 2, and absent in Groups 3 and 4. Replacement resorption was minimal in Groups 1 and 2, and frequent in Groups 3 and 4. Differences between Groups 1 and 2, and between Groups 3 and 4 were not significant, whereas the differences between the two pairs of groups were statistically significant (chi-square and two-way ANOVA, P < 0.006). These results did not support the hypothesis, and questioned the clinical validity of the surface modification in Nd:YAG laser-irradiated dentin. Therefore, the clinical application of Nd:YAG laser to the root surfaces of replanted teeth is not warranted.