OBJECTIVES: This study investigated the relationship between root canal treatment quality and the development and severity of periapical radiolucency in maxillary and mandibular molars using cone beam computed tomography (CBCT). METHODS: A retrospective analysis was conducted on CBCT images of 396 maxillary and mandibular first and second molars. High-quality imaging records confirmed the absence of preoperative periapical lesions, with root canal treatments performed at least 4 years prior. The Periapical and Endodontic Status Scale was used to evaluate root canal filling length and homogeneity, coronal restoration seal, treatment complications, lesion size, relationship between root and lesion, and bone destruction location across axial, sagittal, and coronal CBCT sections. RESULTS: Endodontic treatment quality significantly influenced periapical lesion development, lesion size, relationship between root and lesion, and bone destruction location (p < 0.05). The prevalence of periapical radiolucencies was higher in teeth with short root canal fillings, inadequate filling homogeneity, insufficient coronal restorations, root perforations, or missed canals (p < 0.05). Larger lesions (> 5 mm) correlated with short root canal fillings, inadequate filling homogeneity, and inadequate restorations, which were also associated with cortical bone destruction and furcation involvement (p < 0.05). Apical radiolucency was more frequently observed in mandibular first molars than in second molars, with the lesions tending to be smaller, involving multiple roots, and located around the root structures. CONCLUSION: This study highlights the critical influence of endodontic treatment quality on periapical lesion development, lesion size, relationship between root and lesion, and bone destruction location. Increased lesion severity compromises retreatment success, underscoring the importance of understanding periapical radiolucency risk factors for improved outcomes.