BACKGROUND The aim of this study was to compare the biomechanical properties and the amount of coronal tissue removed among the different access cavities with a multisample 3-dimensional finite element analysis in the mandibular first molar. The correlation between the amount of tissue removed and the fracture resistance of the teeth was also analyzed. METHODS Micro-computed tomography data from 20 2-rooted mandibular first molars were included in this study as 3-dimensional modeling prototypes. Models of untreated molars and molars treated with the traditional access cavity (TradAC), the conservative access cavity (ConsAC), and the straight-line minimally invasive endodontic access cavities (SMIAC) were created. Each model was loaded in 3 ways to simulate the functional conditions of occlusion. The amount of tissue removed and the maximum stress in the cervical region were recorded and analyzed, and the correlation between them was also analyzed. RESULTS The amount of coronal tissue and pericervical dentin (PCD) removed in SMIAC and ConsAC was less than that of TradAC. The mean maximum stress in the cervical region was significantly smaller in SMIAC and ConsAC than in TradAC. The amount of hard tissue and PCD loss was positively correlated with the maximum stress in the cervical region of the tooth. CONCLUSIONS In mandibular first molars, it could be beneficial to improve the fracture resistance of the tooth after endodontic treatment by the minimally invasive access cavity to reduce the loss of coronal tooth tissue and PCD. The SMIAC may be an option balancing biomechanical properties and clinical convenience.