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The purpose of this in vitro study was to test the effect of Ketac-Endo (KE) and AH 26 on resistance to root fracture and also to evaluate the effect of smear layer. Seventy-two human maxillary canine teeth were randomly divided into six groups (n = 12) and were prepared using six different methods: group 1: KE, without smear layer (smear −); group 2: KE, with smear layer (smear +); group 3: AH 26, smear (−); group 4: AH 26, smear (+); group 5 (negative control): nonprepared; group 6 (positive control): prepared but unfilled. After storing 1 week in 100% humidity at 37°C, the coronal lingual walls and root canal spaces were lowered 2 mm below the buccal walls of the roots. The samples were placed into acrylic resin blocks so that 10 mm of buccal roots were exposed and were placed in a specially designed steel pad at an angle of 15 degrees to the long axis of the root. A slowly increasing force was applied at the junction of the buccal wall and root canal space until fracture occurred. The force required to fracture each tooth was recorded as kg and statistically analyzed using one-way analysis of variance and Duncan tests. The results indicated that instrumentation of the root canals significantly weakened the tooth structure to fracture (p < 0.05). The canals obturated with either sealer were significantly stronger than roots whose canals were instrumented but not obturated (p < 0.05), and there was no difference between the sealers. The presence or absence of the smear layer did not cause any significant effect on the root fracture resistance of the teeth (p > 0.05).