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Irrigation and debridement can be a source of iatrogenic injury in open fracture treatment. Although high-pressure pulsatile lavage has been shown to cause considerable damage to bone, little has been written about its effects on soft tissue. The purpose of this study is to quantify and compare the damages on soft tissue caused by high-pressure pulsatile lavage and low-pressure lavage. Forty specimens of fresh ovine muscle were collected and subjected to high-pressure pulsatile lavage or low-pressure lavage, with the delivery orientation being across or in line with the muscle fibers. Ten additional specimens were used as controls. The results show that high-pressure pulsatile lavage causes considerable soft tissue penetration of particulate markers (across, 4.7 mm; in line, 15.6 mm) when compared with low-pressure lavage (across, 0.5 mm; in line, 0.7 mm). Furthermore, all specimens subjected to high-pressure pulsatile lavage showed gross tissue disruption. Fifteen additional samples were obtained to measure cellular death. This was observed at a deeper level for high-pressure pulsatile lavage (median depths: across, 1210 μm; in line, 1335 μm), which was approximately twice that of low-pressure lavage (across, 485 μm; in line, 682 μm). These results show that high-pressure pulsatile lavage penetrates and disrupts soft tissue to a deeper level than low-pressure lavage, causing considerable gross and microscopic tissue disruption.