Aim: This study aims to evaluate and compare the apical sealing ability of different obturation techniques using bioceramic and silicone-based root canal sealers in an in vitro setting. Materials and Methodology: Twenty-five extracted mandibular premolars were standardized to 15 mm root length and instrumented using ProTaper Universal Ni-Ti rotary files. The samples were randomly divided into five groups (n = 5) based on the obturation technique and sealer used. Group 1 and Group 2 were obturated using thermoplasticized gutta-percha with mineral trioxide aggregate (MTA) Fillapex and Ceraseal, respectively. Group 3 and Group 4 utilized bioceramic gutta-percha with MTA Fillapex and Ceraseal, respectively. Group 5 employed single-cone obturation (SCO) with GuttaFlow 2. Apical microleakage was assessed using methylene blue dye penetration, and measurements were analyzed under a stereomicroscope at ×20 magnification using ImageJ software. Statistical analysis was performed using one-way ANOVA (P < 0.05). Results: All groups exhibited varying degrees of apical leakage. Group 5 (GuttaFlow 2 with SCO) demonstrated the lowest mean leakage (0.87 ± 0.26 mm), whereas Group 1 (thermoplasticized gutta-percha with MTA Fillapex) had the highest leakage (2.66 ± 0.61 mm) (P < 0.05). Conclusion: Although none of the sealers completely prevented apical leakage, GuttaFlow 2 with SCO exhibited the most effective sealing ability. The findings suggest that silicone-based sealers may provide enhanced apical sealing in root canal therapy. Further studies with larger sample sizes and clinical validation are warranted. © 2025 Elsevier B.V., All rights reserved.