Background and Objective: The study aimed was to compare the effect of cross-sectional designs of five rotary systems (One Curve, 2Shape, K3-i File, E3 Azure, Neolix), on the shaping ability of the files in simulated resin blocks under controlled conditions with five repeated use. The shaping ability of the files includes the following variables: (1) Longitudinal sectional area difference, (2) Canal wall surface area difference, (3) Canal volume difference, (4) SMI (structure material index) difference, (5) Cross-sectional area difference. Methods: Five rotary file systems: (1) One Curve, (2) 2Shape, (3) K3-i File, (4) E3 Azure, (5) Neolix, were tested in simulated J-shaped root canal resin blocks with a 45˚ angle of curvature. 10 files from each system, each one of the 10 files were used to prepare 5 resin blocks, named R1-R2-R3-R4-R5. All the used files from the 5 systems had tip size 25 diameter, and taper (6%), and length (25 mm). The first 4 rotary systems were used with a fixed speed (350 rpm), and fixed torque (3 Ncm), except for the fifth system which was used with a speed of (500 rpm), and torque (4 Ncm), Following the manufactural recommendation of each system. All the 250 resin blocks were prepared for Glide Path with manual reamers size 10, and 15, with a fixed working length 16 mm, then all the 250 samples were prepared with a Proglider rotary file from Dentsply (size 16 taper 3%), then finally were prepared with Edge Files (USA), with size 20 and taper 6%, reaching to the step of master preparation with the selected files of the 5 systems. Using a customized device for preparation to ensure fixed vertical force and to exclude any lateral force, preparation was done with EDTA solution as irrigation, with a fixed no. of 4 strokes for the first 5 systems and 9 strokes for the Neolix, the time was controlled by using a Metronome, each stroke duration was 6 seconds. Results: In the first, second, third, and fourth variables a statistically non-significant difference (P > 0.05) was found between One curve and 2Shape, a statistically significant difference (P < 0.05) was found between One Curve, K3-i File, E3 Azure, and Neolix. About the fifth variable which is the Cross-sectional area difference: the study compared the difference between the cross-section area of the canal at the point D8, comparing the cross-section area before and after preparation using ANOVA test and Post hoc test, a statistically significant difference (P < 0.05) was found between the Neolix and (2shape, K3 i-File, and E3 Azure). Conclusion: The cross-sectional design of the endodontic rotary instrument had an obvious effect on the shaping ability of the system. Keywords: Cross-sectional design, Shaping ability, Nickle Titanium rotary files (One Curve, 2Shape, K3-i File, E3 Azure, Neolix).