This study aimed to evaluate the safety and efficacy of a method of using nickel-titanium rotary instruments for preparing the C-shaped root canal system. Forty-three human mandibular second molars with a C-shaped canal configuration were prepared with a crown-down approach to an apical dimension of size 30 by using a combination of ProFile and HERO instruments. Micro-computed tomography was used to examine the canal diameter and the remaining thickness of the dentin wall along the root canal. Results showed that only isolated regions in cross section of the C-shaped canal were physically prepared by the rotary instruments. The furcal wall (concave aspect of the "C" in cross section) of all clinically identifiable canals had a similar thickness at a distance 1-7 mm from the apical constriction both before and after instrumentation. More dentin was removed from the outer (convex aspect of the "C") than the furcal aspect at the apical region, but the converse was true more coronally. All prepared canals showed a taper that matched that of the last instrument used. It was concluded that cleaning of the C-shaped canal system is incomplete with the use of rotary instruments and should be assisted by ultrasonic irrigation. Although rotary instruments seemed to be safe in such canals, further enlargement to an apical dimension greater than size 30 (0.06 taper) is not recommended.