The aim of this study was to formulate and evaluate acrylic acid‐based topical hydrogel patches of mupirocin for new pharmaceutical controlled release application. These cross‐linked hydrogel patches were synthesized by modified aqueous‐based polymerization technique. Acrylic acid was cross‐linked with 2‐acrylamido‐2‐methylpropanesulfonic acid (AMPS) with the help of cross‐linker N,N‐methylenebisacrylamide (MBA). Hydrogel patches were characterized by FTIR, TGA, DSC, SEM, swelling behavior, in vitro percent drug release at different pH, permeation across skin, ex vivo drug retention study, and irritation evaluation of mupirocin‐loaded hydrogels. Developed patches were spherical, thick, adhesive and with good elastic strength. FTIR confirmed the cross‐linking and formation of new structure having appropriate characteristics needed for controlled release delivery system. Dug (mupirocin) release through rabbit's skin was evaluated by Franz diffusion cell and up to 3,991.95 μg/L.5 cm2 was permeated, and drug retention in skin revealed substantial retention up to 1,261 μg/L.5 cm2. Formulated hydrogel patches were nonirritant to the skin up to 48 hr as validated by Draize patch test. Enhanced retention of drug in skin demonstrated good potential of topical delivery for skin bacterial infections.