Introduction: In this study, thick polyethersulfone (PES) nanofibrous scaffolds were prepared by fine tuning of electrospinning parameters and was evaluated for wound dressing applications. Materials and Methods: Scanning electron microscopy and Brunauer-Emmett-Teller methods were used for PES nanofibers characterization. The interaction between fibroblasts and nanofibers was studied in vitro. Further, a mouse model was used to evaluate the effectiveness of the PES scaffold in wound healing. Vaseline gauze dressing and a conventional gas permeable bandage were used as a control. The wound repair process was evaluated by histological examination and immunohistochemistry staining using antibodies to cytokeratin 10 (CK10), proliferating cell nuclear antigen (PCNA), and alpha-smooth muscle actin (alpha-SMA). Results and conclusion: The characterization of nanofibers showed that the PES membrane has nanoscle, porous, high surface area structure. These properties conferred higher exudate absorption capacity for the PES scaffold which is essential for effective wound healing. In vitro results indicated that the PES scaffold can support fibroblast proliferation similar to that with tissue culture polystyrene. Epithelial regeneration was expeditiously accelerated under PES as compared with Vaseline gauze. Greater fibroblast maturation, improved collagen deposition and faster edema resolution were the superior properties of PES over the commercial dressing. Based on these results we conclude that the biocompatible PES nanofibers can effectively be used as a dressing to accelerate wound healing.