Purpose <p>to evaluate the efficacy of Erbium: Yttrium-Aluminum-Garnet (Er: YAG), continuous-wave (CW), and pulsed diode laser- activation methods compared to conventional irrigation in removing the smear layer using different concentrations of sodium hypochlorite (NaOCl), saline, EDTA, and EDTA combined with NaOCl root canal irrigants.</p> Methods <p>Three hundred extracted human straight-root, single-canal premolars were decoronated and instrumented using a rotary NiTi system. The samples were randomly divided into five main groups (<i>n</i> = 60 each) according to the method of irrigation activation: Group 1 – conventional, Group 2 – Er: YAG laser-activated, Group 3 – CW diode laser-activated, Group 4–70%-duty cycle, pulsed diode laser-activated, and Group 5–50%-duty cycle, pulsed diode laser-activated irrigation techniques. Each group was further subdivided based on the type of root canal irrigant into 6 subgroups: NaOCl + EDTA, EDTA, 5.25%, 2.5%, and 1% NaOCl, and saline (<i>n</i> = 10 each). Smear layer removal was evaluated using environmental scanning electron microscopy (ESEM) at the coronal, middle, and apical thirds of the root canal.</p> Results <p>Er: YAG laser-activated irrigation achieved significantly superior smear layer removal in all thirds compared to diode laser-activated and conventional methods (<i>p</i> &lt; 0.001). Among irrigants, NaOCl + EDTA was the most effective (<i>p</i> &lt; 0.001), while saline had the least effect. Higher NaOCl concentrations improved smear layer removal with diode and conventional methods, whereas Er: YAG performed better with lower NaOCl concentrations.</p> Conclusion <p>Er: YAG and 976-nm diode laser activations significantly enhance the smear layer removal efficiency of root canal irrigants. NaOCl concentrations can influence the efficacy of conventional and laser-activated irrigations methods.</p>