Cold plasma skin welding is a novel technology that bonds skin edges through soldering without the use of synthetic materials or conventional wound approximation methods such as sutures, staples, or skin adhesives. The cold plasma welding system uses a biological solder applied to the edges of a skin incision, followed by the application of cold plasma energy. The objectives of this study were to assess the feasibility of a cold plasma welding system in approximating and fixating skin incisions compared with conventional methods and to evaluate and define optimal plasma welding parameters and histopathological tissue response in a porcine model.