Cleaning and shaping of the root canal system are essential for the successful outcome of endodontic treatment. In addition to the routinely used irrigating solutions, other technologies have been investigated for the treatment of root canal dentine, such as different types of laser systems. Purpose: The aim of our in vitro study was to evaluate the effect of different types of laser irradiation (Er:YAG , Nd:YAG, diode laser and photodynamic therapy) on the intracanal dentin and their interference in the apical seal of filled root canals. Methodology: 72 human single rooted teeth were randomly assigned into 6 groups. Root canal preparation was done using ProTaper Universal rotary system up to F3. The laser irradiation was performed at the end of the traditional endodontic preparation as a final means of decontaminating the endodontic system. Teeth were filled with a core-carrier system Guttacore (Dentsply, Sirona) and sealer AH- plus. Results: Statistical analysis showed that all groups had significantly less leakage in apical third than the control group. The laser-treated groups presented better results than Group II (Classical disinfection protocol), without statistically significant difference. The morphological changes on the apical intraradicular dentin surface caused by Nd:YAG and Er:YAG laser irradiation resulted at least linear dye apical leakage. Conclusions: Laser irradiation may improve the apical seal of the root canal. Different type of laser systems with appropriate parameters are recommended to be used as an adjunct to the current chemical root canal disinfection protocols.