Introduction: The purpose of this study was to compare the effect of different final irrigation solutions on fracture resistance values (FRVs) of endodontically treated teeth. Methods: Eighty extracted decoronated human incisors were used. Ten randomly selected roots were used as the negative control group. The remaining roots were prepared by the ProTaper system (Dentsply Maillefer, Ballaigues, Switzerland) up to F2. Ten prepared roots were selected as the positive control. The other prepared roots were divided into 6 (n = 10) groups according to the final irrigation solution used: 5 mL saline, 17% EDTA, EDTA with a surfactant (REDTA), chlorhexidine, QMix (Dentsply Tulsa Dental Specialties, Tulsa, OK), and BioPure MTAD (Dentsply Tulsa Dental Specialties). In all groups, the final irrigation was performed for 1 minute except for the BioPure MTAD group; in this group, it was applied for 5 minutes according to the manufacturer's instructions. The specimens were filled with a single gutta-percha cone and AH 26 sealer (Dentsply, De Trey, Konstanz, Germany): After being stored under 37 degrees C and 100% humidity for a week, the specimens were loaded in a vertical direction at 1 mm/min speed until they were vertically fractured. The results were analyzed by the Kruskal-Wallis and Siegel Castellan tests. Results: The negative control group showed the highest FRV. There were statistically significant differences between the negative and positive control groups (P < .05). Specimens irrigated with REDTA and QMix showed a higher FRV compared with the positive control group (P < .05). Specimens exposed to chlorhexidine and BioPure MTAD showed a lower FRV compared with the negative control group (P < .05). Conclusions: Root canal preparation weakens the tooth. The final irrigation regimen has an impact on the FRV. A short time exposure to irrigation solutions (REDTA and QMix) that include surfactants probably contributed to the higher FRV, instead of a long time exposure as done with BioPure MTAD.