Biomechanical preparation of root canal is one of the main endodontic therapy steps. More recently, micro-CT has been proposed to compare the canal anatomy during preparation to give clinicians an impartial evaluation of many rotary systems in the market. The purpose of this study was a micro-CT imaging-based comparison of root canal morphology changes after instrumentation with different Dentsply Sirona NiTi systems (Protaper Gold (PTG), Protaper Next (PTN), Waveone (WO)). PTG is primarily developed for users of ProTaper Universal (PTU) who are reluctant to change their technique but would benefit from the improved safety offered by “gold proprietary processing”. PTN (5th generation of rotary systems) is designed for rotary users who want to reduce the number of files and to use the most advanced swaggering motion. WO (4th generation of rotary systems) is designed for those rotary users who seek simplicity. All the systems have their own advantages and disadvantages. It is the practitioner’s decision to choose the best system that satisfy their requirements and their experience levels. More research conduction is recommended to develop more effective system that would efficiently and quickly clean the entire root canal system with respect to the original anatomy of the canal.