The aim of this study was to assess the effects of intracanal irrigation with sodium hypochlorite (NaOCl) and ethylenediaminetetracetic acid (EDTA) prior to calcium hydroxide medication on the compressive strength of root dentin. Forty-eight roots with single and straight canals were instrumented with a crown-down technique using Flexofile files and Gates Glidden burs, under 0.9% sodium chloride (NaCl) irrigation. Root canals were randomly separated into 4 groups (n=12), according to the irrigating solution: Control Group, 0.9% NaCl; Group NaOCl , 1% NaOCl; Group EDTA , 17% EDTA; and Group EDTA+NaOCl , 17% EDTA and 1% NaOCl. Solutions remained for 40 min, renewed every 10 min, except for Group EDTA+NaOCl , where the solutions were alternated every 10 min. Canals were dried and filled with calcium hydroxide paste, and radiographed. Each canal was sealed and stored at 37 °C for 30 days. After this period, the roots were cut 1 mm below the cementoenamel junction and 6 mm apically from this point in order to obtain 6 mm-long cylinders. The compressive test was conducted with a crosshead speed of 1 mm/min. The means (±SD) (MPa) of compressive strength were: Control Group, 151.23±94.36; Group NaOCl , 167.50±57.25; Group EDTA , 108.79±99.88; Group EDTA+NaOCl , 60.12±92.10. Significant statistical differences among groups were found (ANOVA and Tukey, α=5%, p=0.02). Control Group and Group NaOCl showed higher means of compressive strength than Group EDTA+NaOCl . Intracanal irrigation with 17% EDTA and 1% NaOCl produced a significant reduction of dentin compressive strength 30 days after medication with calcium hydroxide.