Aim <p>This randomized controlled clinical trial evaluated the effectiveness of guided endodontic microsurgery (GEMS) compared to conventional endodontic microsurgery (EMS) in critical anatomy regions.</p> Materials and methods <p>Twenty-eight patients (ages 19–58 years) requiring endodontic microsurgery in critical anatomical regions were randomly allocated to guided surgery (<i>n</i> = 14) using 3D-printed surgical guides with trephine burs or conventional microsurgery (<i>n</i> = 14). Primary outcomes included surgical procedure time. Secondary outcomes were periapical lesion size measured by CBCT at 6, 12 months and success rate at 1-year follow-up and complications. statistical analysis employed independent t-tests and chi-square tests.</p> Results <p>The guided group demonstrated significantly shorter surgical time (18.21 ± 3.45 min vs 26.07 ± 4.29 min) (independent t-test, <i>p</i> &lt; 0.001). Complete lesion resolution at 1 year was achieved in 92.9% of guided cases, compared with 71.4% in conventional cases (chi-square, <i>p</i> = 0.139). No complications were observed.</p> Conclusions <p>Guided endodontic microsurgery using a 3D-printed surgical guide with trephine burs significantly reduces surgical time. The technique demonstrates a clinically relevant trend toward improved healing outcomes, supporting its adoption for complex endodontic surgical cases.</p> Trial registration <p>ClinicalTrials.gov Identifier: NCT05283252</p>