Nickel-titanium (NiTi) usage is associated in endodontics with some complications including canal transportation. Centering ability of a NiTi file is the ability to stay centered in the root canal system during instrumentation. Any undesirable deviation from the natural canal path is indicated as canal transportation. A possible strategy to improve the centering ability of NiTi instruments is the pre-enlargement of the coronal third of the root canal to minimize coronal interferences. This procedure is known as coronal flaring. The aim of this study was to perform a micro-computed tomographic (micro-CT) evaluation of the effect of coronal flaring on canal transportation and centering ability of two heat treated nickel-titanium rotary instruments, 2Shape (Micro Mega, Besançon, France) and HyFlex CM (Coltène Whaledent, Altstätten, Switzerland). Thirty extracted mandibular molars with two independent mesial canals were selected and randomly instrumented (n = 15 canals) with One Flare (Micro Mega, Besançon, France) before HyFlex CM, HyFlex CM (without coronal flaring), One Flare before 2Shape and 2Shape (without coronal flaring). One Flare (Micro Mega, Besançon, France) was introduced 4 mm below the canal entrance for canals prepared with coronal flaring. HyFlex CM and 2Shape were used accordingly to manufacturers’ instructions. New files were used for each canal. During and after instrumentation, irrigation procedures were performed. Micro-CT images were obtained pre- and post-preparation to measure and record root canal transportation and centralization. They were reconstructed from root apex to canal orifices, generating approximately 1000 sections per specimen. The anatomical thirds were determined by dividing the number of cross-sectional slices by three. Root canal transportation and centralization were determined by Gambil method, and the mean values were analyzed by repeated measures analysis of variance followed by multiple comparisons of Bonferroni to compare the different instrumentations procedures and the root thirds (p < 0.05). As for root canal transportation, 2Shape reported significantly higher values compared to HyFlex CM in the cervical region independently from the coronal flaring. In the apical region, 2Shape caused significantly minor canal transportation when used with coronal flaring with compared with the absence of coronal flaring. Regarding the centralization, HyFlex CM showed higher values than 2Shape in the cervical, independently from coronal flaring. In the apical region, 2Shape with coronal flaring exhibited significant major centering ratio, compared with not. Within the limitations of this study, coronal flaring reduced canal transportation and improved centralization of the 2Shape files in the apical section while it had no significant influence on shaping ability of the HyFlex CM instruments. Coronal flaring could represent a valid strategy to improve the shaping ability of NiTi files knowing that its benefit could be influenced by the shaping file used.