Objective: To evaluate the effect of diode laser irradiation on crystallographic and morphologic characteristics of root canal walls after final irrigation with either 17% EDTA or BioPure MTAD. Method and Materials: Root canals in 60 single-rooted teeth were instrumented using a rotary Ni-Ti system. The teeth were randomly divided into three groups (n = 20) based on the final irrigants: group 1, saline; group 2, 17% EDTA; and group 3, MTAD. Each group was further divided into two subgroups (n = 10). Subgroup A received diode laser irradiation at a wavelength of 810 nm and an output power of 2 W for 5 × 5 seconds, while subgroup B received no irradiation. A paired t test was used to compare mean dentinal erosion before and after irradiation in each group. Specimens were analyzed using SEM and x-ray diffractometery. One-way ANOVA and a post hoc Tukey test were used to evaluate dentinal erosion between groups. Kruskal-Wallis and Mann-Whitney U tests were used to evaluate any significant differences in the amount of dentin erosion between the groups. Results: SEM micrographs showed closed dentinal tubules in the control group, while in unlased BioPure MTAD and EDTA groups, clean root canal walls were evident. Erosion was mostly seen in EDTA-treated teeth, while an increase of erosion degree was noted on root canal walls after additional laser irradiations. After irrigation and laser irradiation, the XRD spectrums indicated sharper peaks of EDTA, which showed a slight crystallographic change compared with the other groups. EDTA made changes in the mineralization of dentin due to its higher accumulation on the dentinal wall surface and produced significant degrees of erosion in comparison with MTAD by changing the physical properties of the root canal wall surface. These undesirable changes can be enhanced by further laser irradiation. Conclusion: Results confirm that a diode laser in combination with BioPure MTAD have minimum effect on the chemical properties of root canal dentin while having good smear layer removal properties. The results of the present study indicated that a diode laser in combination with Biopure MTAD might be suggested as a final management of the root canal system prior to canal obturation. Keywords: diode laser, EDTA, MTAD, SEM, x-ray diffraction