Abstract Introduction The manufacturer of the Hyflex CM endodontic files claims the files remain centered within the canal, and if unwound during treatment, they will regain their original shape after sterilization. The purpose of this study was to evaluate and compare the canal centering ability of the Hyflex CM and the ProFile ISO filing systems after repeated uses in simulated canals, followed by autoclaving. Methods Sixty acrylic blocks with a canal curvature of 45° were stained with methylene blue, photographed, and divided into 2 groups, H (Hyflex CM) and P (ProFile ISO). The groups were further subdivided into 3 subgroups: H1, H2, H3; P1, P2, P3 (n = 10). Groups H1 and P1 were instrumented to 40 (.04) with the respective file system. Used files were autoclaved for 26 minutes at 126°C. After sterilization, the files were used to instrument groups H2 and P2. The same sterilization and instrumentation procedure was repeated for groups H3 and P3. Post-instrumentation digital images were taken and superimposed over the pre-instrumentation images. Changes in the location of the center of the canal at predetermined reference points were recorded and compared within subgroups and between filing systems. Results Statistical differences in intergroup and intragroup transportation measures were analyzed by using the Kruskal-Wallis analysis of variance of ranks with the Bonferroni post hoc test. There was a difference between Hyflex CM and ProFile ISO groups, although it was not statistically significant. Intragroup differences for both Hyflex CM and ProFile ISO groups were not significant (P < .05). Conclusions The Hyflex CM and ProFile ISO files equally maintained the original canal's morphology after 2 sterilization cycles.