The initial management of open fractures often requires repeated irrigation and debridement of the open wound and stabilization of the fracture. However, washing out the fracture hematoma could delay the early healing process of stable fractures. Because delayed union and non-union are serious complications, the effect of repeated irrigation and debridement on the fracture healing process was investigated. Twenty-four rabbits received unilateral, transverse. mid-tibial open osteotomies with a 3 mm gap. The osteotomy site was thoroughly irrigated and stabilized with double-bar external fixators. The osteotomy sites in the study groups underwent repeat irrigation and debridement on either the third day (Group II), the fourth day (Group III), or consecutively on the first and second days (Group IV) after the index procedure. The bone healing was assessed with weekly radiographs and peripheral quantitative computerized tomographs. In Group I (control), all osteotomies healed radiographically before the tenth week. In Group II, five out of six osteotomies healed radiographically before the tenth week. In Group III, only two of five osteotomies healed before the tenth week. In Group IV, none of the osteotomies had healed by week fifteen. All of the non-healed osteotomies exhibited atrophic non-unions at fifteen weeks. Compared to the control group at the tenth week, the average bone mineral content at the osteotomy site and the area of high mineral density callus (> or = 890 mg/cm3) were significantly lower in Groups III (63%, p = 0.002 and 95%, p = 0.05, respectively) and IV (99%, p < 0.001 and 100%, p = 0.05, respectively). The results of this study suggest that repeated irrigation and debridement, associated with persistent rigid immobilization, may contribute to the development of delayed unions or atrophic non-unions.