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Background/Objectives: Guided endodontic microsurgery is a novel approach designed to improve safety and precision compared with conventional freehand techniques. The present study aimed to evaluate the accuracy, stability, and operative time of trephina-tions performed using stereolithographic surgical guides designed with Blue Sky Plan and Exoplan software compared with the conventional technique. Methods: A comparative in vitro study was conducted on 72 roots from 12 stereolitho-graphic mandibles. CBCT (Hyperion X9) and STL intraoral scans were superimposed to design 16 surgical guides with verification windows and metallic sleeves for 4.45 mm trephines. Roots were assigned to three groups: conventional control, Blue Sky Plan, and Exoplan. Stability was assessed by displacement >0.5 mm, accuracy was measured by CBCT superimposition to calculate deviation from a 3 mm apical resection target, and operative time was recorded in seconds. Statistical analysis included Kruskal–Wallis, chi-square, and ANOVA tests. Results: Blue Sky Plan exhibited 50% of guides with instability (>0.5 mm mobility) compared with 12.5% in Exoplan (p > 0.05). Exoplan showed the lowest mean deviation (0.17 mm), outperforming control (1.16 mm) and Blue Sky (0.55 mm), with significant differences confirmed by Kruskal–Wallis (p = 0.000). Operative time was shortest with Exoplan (106 s), followed by Blue Sky (127 s) and control (155 s), with statistically sig-nificant differences. No correlation was observed between accuracy and operative time. Conclusions: Exoplan guides demonstrated superior overall performance by combining improved stability, accuracy, and efficiency compared with both Blue Sky Plan and the conventional technique. These results support guided apical surgery as a tool to enhance safety, predictability, and efficiency in endodontic practice, though further clinical validation is needed.