BACKGROUND The purpose of this study was to evaluate and compare 2 different access cavity designs in combination with 2 popular single-file preparation systems to see which combination preserves dentin, more specifically pericervical dentin, best. The minimum remaining dentin thickness and dentin volumes were evaluated pre- and postinstrumentation. METHODS Sixty extracted human mandibular molars were selected and randomly divided into 2 different access cavity design preparation groups: traditional access cavities (n = 30) and conservative access cavities (n = 30). Within each cavity preparation design group, the 30 teeth were divided into 2 instrumentation groups (WaveOne Gold Primary; Dentsply Sirona, Ballaigues, Switzerland [n = 15] and TruNatomy Prime, Dentsply Sirona [n = 15]). Samples were scanned using micro-computed tomographic imaging before and after access cavity preparation as well as after final endodontic instrumentation. The pericervical remaining dentin thickness and dentin volume changes were evaluated and compared. RESULTS Conservative access cavity designs resulted in more favorable remaining dentin thickness. The least amount of mean dentin volume loss was also recorded in the conservative access cavity preparation groups regardless of the preparation instrumentation. CONCLUSIONS In terms of the remaining pericervical dentin thickness and dentin volume reductions, the authors conclude that conservative access cavity designs preserve dentin best.