Objective: Low-frequency ultrasound debridement with irrigation is an effective method of wound bed preparation. A recent clinical study compared hypochlorous acid preserved wound cleanser (HAPWOC) to saline and found HAPWOC to be a more effective adjunct to low frequency ultrasound debridement. However, HAPWOC has an added cost. The primary objective of this study was to assess the cost-effectiveness of HAPWOC as an irrigation modality with low-frequency ultrasound debridement for the treatment of severely complex wounds that were destined to be closed primarily via a flap. The secondary objective of this study was to estimate the number needed to treat (NNT) to avoid a wound-related complication and its expected cost per NNT. Methods: A patient-level Monte-Carlo simulation model was used to conduct a cost-effectiveness analysis from the US health system perspective. All clinical data were obtained from a prospective clinical trial. Cost data were obtained from the publicly available data sources in 2021 US dollars. The effect measure was the avoidance of wound-related complications at 14-days post-debridement. The primary outcome was the incremental cost-effectiveness ratio (ICER), a measure of the additional cost per benefit. The secondary outcomes were the NNT and expected cost per NNT to avoid one complication (complementary to the ICER in assessing cost-effectiveness). Deterministic and probabilistic sensitivity analyses (PSA) were performed to gauge the robustness and reliability of the results. Results: The ICER for HAPWOC versus saline irrigation was US$90.85 per wound complication avoided. The expected incremental cost per patient in the study and effect was US$49.97 with 55% relative reduction in wound-related complications at day 14 post debridement procedure. The NNT and cost per NNT were 2 and US$99.94, respectively. Sensitivity analyses demonstrated that these results were robust to variation in model parameters. Conclusion: HAPWOC was a cost-effective strategy for the treatment of complex wounds during ultrasonic debridement. For every two patients treated with HAPWOC, one complication was avoided.