Aim: Cone beam computed tomography (CBCT) is the most refined and affordable method available today for the examination of an incoming patient for different dental pathologies. The aim of this paper is to evaluate the significance of some factors influencing the prevalence of apical periodontitis. Materials and methods: An ortopantomography (OPT) and CBCT scan of the dental arches were examined for each of the selected 45 patients. The presence of apical periodontitis (AP) was compared for CBCT and OPT examination. Sensitivity, specificity, predictive values, and accuracy were calculated for CBCT, using OPT as a reference. The impact of protective/risk factors on the development of AP was examined. Results: CBCT showed higher sensitivity (250%), predictive values (111%), accuracy (111%), and specificity (101%) than OPT. It was found to have higher sensitivity in all the dentition areas, especially where empty anatomical spaces or more radiotransparent structures have a strict relationship with the tooth apex and periapical structures like upper front area, premolar areas, and, especially, in the upper molar area. The prevalence of AP increased from 16 to 17% in the case of insufficient conservative restoration or 25% in the case of microleakage, 35–42% in the case of prosthetic restoration, 56–67% for posts, and 60 and 85%, respectively, for inadequate endodontic treatment and missed canals. Conclusion: CBCT plays a decisive role in the evaluation of molar areas and in the endodontic treatment planning, when a close relationship between the apex and important anatomical structures exists. Different risk factors with different relevance are identified. Clinical significance: As CBCT-examined results show, coronal restorations are moderate-risk factors, while insufficient endodontic treatments and posts are high-risk factors for the development of AP.