Purpose: The present study was performed to examine the morphological and compositional changes of human dentin after Er:YAG laser irradiation by light microscopy (LM), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and energy dispersive x-ray spectroscopy (SEM-EDX). Materials and Methods: Twenty-five dentin specimens were prepared and subjected to Er:YAG laser irradiation at 200 mJ (25.5 J/cm²) energy density; 20 were irradiated under continuous water cooling (spray, 1 mL/min) and 5 were irradiated without water spray. Five samples with water mist and 5 without were observed with SEM. Five samples with water mist were observed with TEM and the remaining 10 samples were examined by SEM-EDX. Results: SEM examination revealed a scaly or irregular surface after Er:YAG laser irradiation with water mist and an absence of a smear layer; the orifices of dentinal tubules were exposed. Irradiation without water mist produced molten amorphous structures; severe melting or cracking of the dentin was observed. TEM observation of cross sections of lased dentin presented three different zones: one of complete ablation, an ablation zone of mineral components, and an unaffected zone. The results of x-ray spectroscopy showed that the quantities of Ca (Ca weight %) and P (P weight %) were significantly greater in the lased surface. However, no significant differences were found between the Ca:P ratio of irradiated and nonirradiated areas. Conclusions: Some favorable morphological changes of the dentin were achieved by Er:YAG laser irradiation.