This study evaluated the effect of the use of EDTA solution at various intervals to remove intracanal calcium hydroxide medication on fracture resistance. One hundred and one extracted lower premolar teeth were randomly allocated into one control group (n = 5), two main experimental groups (CH(+), with calcium hydroxide dressing, and CH(−), without calcium hydroxide dressing), with four subgroups (EDTA intervals: 1 min, 3 min, 5 min, 10 min, n = 12). Ready-to-use injectable calcium hydroxide was used for the samples in the four CH(+) subgroups, and the samples were kept in an incubator at 37 °C and 100% humidity for seven days. All samples (CH(+), CH(−)) were irrigated with 17% EDTA, which was accompanied by activation with EndoActivator for 1, 3, 5, and 10 min, and then rinsed with 2.5% NaOCl in a standardized manner. The obturation was conducted using the warm obturation technique; experiments were conducted with a universal testing device, and their fracture strength was recorded. Compliance with the normal distribution was examined with ±2 skewness coefficients. Two-way ANOVA, Tukey’s, one-way ANOVA, and Dunnett’s tests were used for statistics (p < 0.050). A statistically significant difference was found between the mean values of the force between the groups (p = 0.009). The mean strength of the tooth at fracture that CH(−) was 401.7, CH(+) was 335.35. There was no statistically significant difference between the mean values of the forces according to time intervals (p = 0.387). While there was no significant difference among the experimental groups (p = 0.229), the mean fracture strength of the negative control group was found to be significantly higher (p < 0.001). The highest fracture resistance was observed in the nonprepared group. Irrigation with EDTA for up to 5 min showed more acceptable fracture resistance results than the other groups. Using calcium hydroxide significantly and negatively affected the root strength.
