Objectives <p>The objective of this study is to evaluate the incidence and volume of contrast medium extrusion when activated with a laser and to compare these outcomes with those of other irrigation techniques.</p> Materials and methods <p>Sixteen cadaver mandibles containing 116 single-rooted teeth were prepared using conventional rotary instrumentation. The teeth were randomly assigned to four irrigation groups: side-vented needle, sonic irrigation, laser activation at the orifice, and laser activation at the middle third of the canal. Gastrografin, an iodinated contrast medium, was used to simulate irrigants. Cone Beam Computed Tomography (CBCT) scans were obtained pre- and post-irrigation to assess the incidence and volume of extrusion. Two blinded observers evaluated the images for the presence or absence of extrusion. Data were statistically analyzed using ANOVA and chi-square tests.</p> Results <p>The observers reached a consensus on 116 out of 116 cases, resulting in a percent agreement of 100%. None of the experimental groups, side-vented needle (<i>n</i> = 29), sonic irrigation (<i>n</i> = 29), laser activation at the orifice (<i>n</i> = 29), and laser activation in the middle third (<i>n</i> = 29), demonstrated any radiographic evidence of extrusion.</p> Conclusion <p>This cadaver-based model, combined with CBCT, provides a clinically relevant assessment of irrigant behavior during endodontic treatment. While the findings from this study suggest that LAI at the orifice or in the middle third of the canal may be a safe method for enhancing irrigation in endodontics, clinicians should remain cautious regarding the potential risks of irrigant extrusion.</p>