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Introduction. Negative pressure wound therapy (NPWT) is applied using a foam dressing and an adhesive acrylic drape to create a seal. Removal of this drape can be painful and may play a role in periwound skin breakdown during dressing changes. A novel silicone-acrylic hybrid drape (HA-drape) has been developed for use with NPWT to allow for repositioning after initial placement and easier removal. Objective. This retrospective case series reports on the use of HA-drape in 4 patients who experienced periwound skin breakdown. The goal was to minimize skin breakdown while maintaining a seal on the dressing. Materials and Methods. Four patients with mild to moderate periwound skin breakdown were selected to receive NPWT with HA-drape. Negative pressure wound therapy was applied using a reticulated open cell foam dressing followed by placement of HA-drape to create a seal. Negative pressure wound therapy was initiated at -125 mm Hg with dressing changes occurring every 2 days. Wound healing, periwound healing, and patient-reported pain were assessed at dressing changes. Results. All 4 patients showed significant periwound skin improvement after the first dressing change. All patients reported a decrease in pain with dressing removal. Conclusions. In these 4 patients' wounds, use of NPWT with HA-drape resulted in intact periwound with improved periwound skin healing and reduction in patient-reported pain associated with dressing changes.