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Background: Eccentric instruments have been proposed as more effective and less time‐consuming for endodontic instrumentation. Aim: To compare biomechanical outcomes of different instrumentation systems and time undertaken for instrumentation in resin prototypes. Design: Sixty standardized prototypes of mandibular second primary molars were instrumented according to the following systems: K‐files, ProTaper Next (PTN), XP‐endo Shaper (XPS), XP‐endo Finisher (XPF), XP–Clean (XPC), and Sequence Baby File (SBF; n = 10/each). Irrigation was performed with saline with simultaneous aspiration, and time spent was recorded. The prototypes were micro‐CT‐scanned before and after the instrumentation, and image sets were reconstructed and registered. Non‐instrumented areas, accumulated debris, removed root material volume, and canal transportation were quantified. Data were analyzed through ANOVA, the Kruskal–Wallis test, and the Wilcoxon signed‐rank test (α = 5%). Results: K‐files and SBF resulted in more instrumentation time (p <.05). SBF, XPC and PTN removed less root dentine (p <.05), but PTN left more untouched areas (p <.05). Accumulated debris were lower for XPC and SBF (p <.05). Canal transportation was similar among the groups. Conclusion: Rotary systems reduced instrumentation time, whereas SBF and XPC resulted in more conservative instrumentation, with less debris accumulation and non‐instrumented areas. A dedicated paediatric endodontic system (SBF) outperformed eccentric instruments in terms of effectiveness. [ABSTRACT FROM AUTHOR]