Aim:This ex vivo study was designed to evaluate and compare different endodontic irrigation and activation systems, the self-adjusting file (SAF) instrumentation/irrigation system, and XP-endo finisher for removal of intracanal smear layer.Materials and Methods:Fifty recently extracted, noncarious human intact single-rooted premolars were selected and divided into five groups (n = 10) according to the root canal irrigation systems; syringe and needle irrigation, passive ultrasonic irrigation (PUI), EndoVac irrigation system, SAF system, and XP-endo finisher. All groups were prepared to apical size F4 file except for the SAF group which was prepared to apical size 20 K-file and then instrumented with the SAF file. Each sample was subjected to final irrigation using different irrigation/activation systems. After splitting the samples, one half of each root was selected for examination under scanning electron microscope. The irrigation systems were compared using the Fisher's exact test with significance set at P < 0.05.Results:In the coronal part, there was no difference among the groups. In the mid-root section, the results of the PUI, EndoVac, SAF, and XP-endo finisher groups tended to be better than syringe and needle irrigation, but the difference was not significant. The apical part of the canal, the SAF system, and XP-endo finisher group seemed to be cleaner than those of the EndoVac group, but this difference was not significant.Conclusions:Within the limitations of the present study, SAF system and XP-endo finisher group cleaned the apical part of the canal more efficiently than EndoVac, PUI, and syringe and needle irrigation.