This study aimed to compare three endodontic rotary systems. The new Genius Proflex (25/0.04), Vortex Blue (25/0.04), and TruNatomy (26/0.04v) instruments (n = 41 per group) were analyzed regarding design, metallurgy, and mechanical performance, while shaping ability (untouched canal walls, volume of removed dentin and hard tissue debris) was tested in 36 anatomically matched root canals of mandibular molars. The results were compared using one-way ANOVA, post hoc Tukey, and Kruskal–Wallis tests, with a significance level set at 5%. All instruments showed symmetrical cross-sections, with asymmetrical blades, no radial lands, no major defects, and almost equiatomic nickel–titanium ratios. Differences were noted in the number of blades, helical angles, cross-sectional design, and tip geometry. The Genius Proflex and the TruNatomy instruments had the highest and lowest R-phase start and finish temperatures, as well as the highest and lowest time and cycles to fracture (p p p > 0.05). No differences among tested systems were observed regarding the maximum torque, angle of rotation prior to fracture, and shaping ability (p > 0.05). The instruments showed similarities and differences in their design, metallurgy, and mechanical properties. However, their shaping ability was similar, without any clinically significant errors. Understanding these characteristics may help clinicians to make decisions regarding which instrument to choose for a particular clinical situation.