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Solution blow spinning (SBS) is used to prepare polysulfone materials (PSf) with different morphologies changing the processing conditions. Morphological study is done by scanning electron microscopy. Materials mainly constituted by beads and fibers are obtained. An optimization strategy based on desirability function approach together with Box–Behnken design is employed to find the best processing conditions to produce PSf materials with tailored morphology. Feed rate and air pressure are the variables of SBS processing conditions with the highest influence on the relative amount of fibers produced while air pressure and a particular balance between work distance and feed rate have the highest impact on the size of fibers. Contact angle measurements are used to understand SBS PSf wettability as a function of morphology. It is demonstrated the possibility of designing PSf materials with particular wettability behavior induced by tailored morphologies obtained from a particular election of SBS processing conditions.