ABSTRACT Objectives: The aim of this study was to compare the amount of apically extruded debris during preparation with ProTaper Universal (Dentsply Maillefer, Ballaigues, Switzerland), ProTaper Next (Dentsply Maillefer), a reciprocating single-file (WaveOne; VDW GmbH, Munich, Germany), and a self-adjusting file (SAF; ReDent Nova, Ra'anna, Israel). Materials and Methods: Fifty-six intact mandibular premolar teeth were randomly assigned to four groups. The root canals were prepared according to the manufacturers’ instructions using the ProTaper Universal, ProTaper Next, WaveOne, and SAF. Apically extruded debris was collected in preweighted Eppendorf tubes during instrumentation. The net weight of the apically extruded debris was determined by subtracting the preweights and postweights of the tubes. The data were statistically analyzed using the one-way analysis of variance and the least significant difference tests at a significance level of P < 0.05. Results: A measurable amount of debris was apically extruded in all groups, and the amounts of debris extrusion in the groups were statistically significant (P < 0.001). The ProTaper Next and WaveOne groups resulted in less debris extrusion than the ProTaper Universal group (P < 0.05), and the SAF group resulted in the least debris extrusion. Conclusions: Within the limitations of the present study, it can be concluded that all systems extruded debris beyond the apical foramen.