Technical Abstract: Electrospun chitosan nanofibers were deposited onto atmospheric plasma treated cotton gauze to create a novel composite bandage with higher adhesion, better handling properties, enhanced bioactivity, and moisture management. Plasma treatment of the gauze substrate was performed to improve the durability of the nanofiber/gauze interface. The chitosan nanofibers were electrospun at 3–7% concentration in trifluoroacetic acid. The composite bandages were analyzed using peel, gelbo flex, antimicrobial assay, moisture vapor transmission rate, X-ray photoelectron spectroscopy (XPS), absorbency, and air permeability tests. The peel test showed that plasma treatment of the substrate increased the adhesion between nanofiber layers and gauze substrate by up to four times. Atmospheric plasma pretreatment of the gauze fabric prior to electrospinning significantly reduced degradation of the nanofiber layer due to repetitive flexing. The chitosan nanofiber layer contributes significantly to the antimicrobial properties of the bandage. Air permeability and moisture vapor transport were reduced due to the presence of a nanofiber layer upon the substrate. XPS of the plasma treated cotton substrate showed formation of active sites on the surface, decrease in carbon content, and increase in oxygen content as compared to the untreated gauze. Deposition of chitosan nanofibers also increased the absorbency of gauze substrate.