Aim of the study was to develop a standardized model system to investigate endodontic irrigation techniques and assess the efficiency of different activation methods on the removal of hard tissue debris in complex root canal systems. Mesial roots of mandibular molars were firstly scanned by micro-computed tomography (mu CT) and allocated to three groups of irrigant activation: sonic activation (EDDY, VDW, Munich, Germany), laser activation (AutoSWEEPS, FOTONA, Ljubljana, Slovenia) and conventional needle irrigation (control). Roots were fixed in individual 3D-printed holders to facilitate root canal enlargement under constant irrigation with NaOCl (5%). To enable standardized quantification of remaining debris, BaSO4-enriched dentine powder was compacted into the canals, followed by another mu CT-scan. The final irrigation was performed using 17% ethylenediaminetetraacetic acid (EDTA) and 5% sodium hypochlorite (NaOCl) with the respective activation method, and the volume of remaining artificial debris was quantified after a final mu CT-scan. The newly developed model system allowed for reliable, reproducible and standardized assessment of irrigation methods. Activation of the irrigant proved to be significantly more effective than conventional needle irrigation regarding the removal of debris, which persisted particularly in the apical third of the root canal in the control group. The efficiency of irrigation was significantly enhanced with laser- and sonic-based activation, especially in the apical third.