INTRODUCTION: Hard-tissue debris is accumulated during rotary instrumentation. This study investigated to what extent a calcium-complexing agent that has good short-term compatibility with sodium hypochlorite (NaOCl) could reduce debris accumulation when applied in an all-in-one irrigant during root canal instrumentation. METHODS: Sixty extracted mandibular molars with isthmuses in the mesial root canal system were selected based on prescans using a micro-computed tomography system. Thirty teeth each were randomly assigned to be instrumented with a rotary system and irrigated with either 2.5% NaOCl or 2.5% NaOCl containing 9% (wt/vol) etidronic acid (HEBP). Using a side-vented irrigating tip, 2 mL of irrigant was applied by 1 blinded investigator to the mesial canals after each instrument. Five milliliters of irrigant was applied per canal as the final rinse. Mesial root canal systems were scanned at high resolution before and after treatment, and accumulated hard-tissue debris was calculated as vol% of the original canal anatomy. Values between groups were compared using the Student's t test (α < .05). RESULTS: Irrigation with 2.5% NaOCl resulted in 5.5 ± 3.6 vol% accumulated hard-tissue debris compared with 3.8 ± 1.8 vol% when HEBP was contained in the irrigant (P < .05). CONCLUSIONS: A hypochlorite-compatible chelator can reduce but not completely prevent hard-tissue debris accumulation during rotary root canal instrumentation.