INTRODUCTION: A desirable characteristic of root canal irrigants is the ability of dissolving soft tissues. Sodium hypochlorite, an antibacterial and tissue solvent irrigant used in endodontic treatment is known to be toxic for periapical tissues. Chlorhexidine gluconate, an effective antimicrobial agent, is another irrigant with limited tissue dissolving ability. A mixture of a tetracycline isomer, an acid, and a detergent (MTAD), has recently been introduced as an alternative irrigant in root canal therapy. The purpose of this study was to evaluate the tissue dissolving effect of these root canal irrigants on bovine pulp tissue. MATERIALS AND METHODS: Fifty pieces of bovine pulp tissue 80 mg each were treated with either normal saline, MTAD, 2% chlorhexidine gluconate, 2.6% NaOCl or 5.25% NaOCl for 10 min at 37°C. Desiccated pre-treatment and post-treatment weights of samples were compared. Using Kruskal-Wallis and Mann-Whitney U tests, data was analyzed. RESULTS: Tissue dissolution effect of 5.25% NaOCl (85.98%) was statistically greater than that of all other solutions (P<0.05). Chlorhexidine gluconate had the weakest dissolution effect, and dissolved only 9.36% of the sample tissue. No significant differences were observed between the dissolution effects of normal saline or MTAD. CONCLUSION: Based on the results of this study, the use of NaOCl as intracanal irrigation during instrumentation is recommended, because of its greater tissue dissolution effect.