Aim: The aim of this study is to evaluate and compare the shaping ability of HyFlex™ EDM (HFEDM) and ProTaper Next (PTN) rotary instruments in curved root canals by using micro-computed tomography (micro-CT) imaging. Materials and methods: A total of 22 mandibular molar teeth having separate mesial canals with 20 to 30° curvatures were randomly divided into two groups and instrumented with HFEDM (OneFile) or PTN (X1 and X2). Pre- and post-instrumentation micro-CT scans were obtained. Mesiodistal canal transportation and centering ability were evaluated in four cross-sections (2, 4, 6, and 8 mm from apex). Changes in canal volume and surface area were measured for a 10-mm standardized area of interest. Kolmogorov–Smirnov and Shapiro–Wilk tests were used to assess the normality and homogeneity. Independent and paired t tests and one-way ANOVA were used to analyze data at the p < 0.05 level. Results: Compared to PTN, HFEDM showed significantly less mesiodistal canal transportation and improved centering ability in cross-section L6 (p < 0.05). The instruments showed similar increases in volume and surface area of the canals, with minor insignificant differences. Conclusion: HFEDM and PTN files were safe to use in curved canals and showed similar shaping ability, while respecting the original anatomies. HFEDM OneFile performed better at the vicinity of the danger zone in terms of mesiodistal canal transportation and centering ability.