Silver sulfadiazine (SSD) is the antibacterial of choice for the treatment of burn. The current marketed formulation of SSD is 1% w/w water soluble cream, which requires frequent applications, which is very painful to patients. Niosomes were prepared by a thin film hydration method. The in vitro antimicrobial efficiency of niosomal SSD (18 ± 0.5 mm) was as good as that of marketed cream (17 ± 0.5 mm) against Staphylococcus aureus even when used in half the concentration (0.5%) of marketed cream (1%). Further SSD (0.5% w/w) niosomal gel was prepared using 1.6% carbopol 934. It was evident through in vitro permeation studies that SSD release was considerably retarded from both niosomes and niosomal gel in comparison with marketed cream thereby decreasing the dosing frequency. In-vivo study demonstrated that a niosomal gel containing 0.5% w/w SSD was more effective in burn wound healing compared to 1% w/w marketed cream even when applied once a day.