Introduction: To evaluate the effectiveness of QMix solution (Dentsply Tulsa Dental Specialties, Tulsa, OK) on the smear layer using the following irrigation activation techniques: the EndoActivator (EA) system (Dents ply Tulsa Dental Specialties), photon-initiated photoacoustic streaming (PIPS), and an Er:YAG laser with an endodontic fiber tip. Methods: Sixty-four extracted single-rooted human teeth were decoronated and the canals instrumented with ProTaper (Denstply Maillefer, Ballagues, Switzerland) up to size F4. The canals were irrigated with 5.25% sodium hypochlorite and a saline solution for 1 minute each. The specimens were then divided randomly into 4 experimental and 4 control groups (n = 8) according to the final irrigation activation technique. These groups included group 1, 2.5 mL QMix; group 2, QMix + EA; group 3, QMix + PIPS; and group 4: QMix +. Er:YAG. Laser activated distilled water was used as control groups 5, 6, 7, and 8. Teeth were split longitudinally, and specimens were observed under a scanning electron microscope. Images were taken at the coronal, middle, and apical thirds of the teeth at a magnification of 1000x and were scored in the presence of the smear layer. Data were analyzed with Kruskal-Wallis and Mann-Whitney U tests. Results: The highest scores were found in the apical third of all groups (P < .05). The QMix + Er:YAG group removed the smear layer more effectively than the nonactivated QMix group in the apical third (P < .05). The QMix + EA group removed the smear layer significantly in all thirds of the teeth when compared with the nonactivated QMix group (P < .05). The QMix + PIPS group showed a significantly better effect than the QMix group in the coronal third (P < .05). Conclusions: The EA and Er:YAG laser enhanced the smear layer removal ability of QMix in the apical thirds of the canals. QMix removed more smear layer in the coronal thirds when activated with the PIPS technique.