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Objective: To comprehensively assess the association between operative positioning with intraoperative-acquired pressure injury (IAPI) development., Methods: This retrospective cohort study included 455 patients who underwent surgery between October 2020 and January 2021. The authors grouped patients by operative positioning into the prone position and nonprone position groups. They used propensity-score matching at a 1:2 ratio to control for preoperative confounders, applied multiple logistic regression models to analyze the effects between positioning and IAPI, and assessed interactions of positioning and intraoperative factors on IAPI., Results: The final enrollment was 92 cases in the prone position group and 181 in the nonprone position group. Multivariable logistic analysis suggested that the prone position had a 2.92 times higher risk of IAPI than the nonprone position (odds ratio, 2.92; 95% CI, 1.13-7.57; P = .026). Subgroup analysis showed a significant multiplicative interaction between positioning and foam dressing on IAPI (P < .05), which was not observed in other intraoperative factors (P > .05)., Conclusions: This study provides evidence that prone operative positioning can increase IAPI risk. Patients in the prone position may particularly benefit from using dressings in Chinese populations. Further large-sample longitudinal studies are required to confirm these findings., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)