<p>Traditional Polyurethane (PU) foams have limitations in absorbency and moisture retention. There is a need for advanced wound dressings that can effectively manage wound exudate and maintain an optimal healing environment. This study aims to address these limitations by formulating a highly absorbent, hydrophilic PU foam that can enhance wound care outcomes. The foams were prepared with varying concentrations of Specflex^® NE 434 (isocyanate), Caradol SC56-18&#xa0;S™ (polyether polyol) and HPMC 4&#xa0;K (hydrophilic polymer). Three critical formulation variables/ factors were identified, namely concentration of polyol, HPMC 4&#xa0;K and curing temperature and considered for Box-Behnken experimental design. Seventeen PU foam samples were prepared and tested for their water absorption capacity, density and compression strength, to generate an optimized solution. The optimized foam was assessed for mechanical strength, water vapor transmission rate, absorption rate test, and shape, internal structure, and porosity. The optimized PU foam exhibited water absorption of 490.14%, density of 190.50&#xa0;g/cm³, and compression strength of 1150.50 kPA. Furthermore, Scanning Electron Microscopy results confirmed the highly porous interior sample and micro-computed tomography (Micro-CT) revealed a porosity of 18%. The performance of the newly developed foam was also compared with a commercial polyurethane foam dressing. The results indicated that the hydrophilic polyurethane foam exhibited superior water absorption and optimal water vapour transmission, making it suitable for application on various wound types. The foam’s safety for topical application was confirmed by in vivo skin irritation testing conducted on albino rabbits, which revealed no evidence of irritation. According to the study’s findings, hydrophilic PU foam shows promise as a material for wound care since it promotes healing and creates the ideal moist environment.</p> Graphical abstract <p></p>