<p>Industrial-scale microfiltration (MF) membranes serve a variety of purposes, including pre-treatment processes, the removal of micro-particles, the reduction of turbidity, and sedimentation potential of water in reverse osmosis (RO) and nanofiltration (NF) systems. While CA membranes are of particular interest to researchers in the membrane field due to their outstanding properties, these membranes usually show non-uniform pores. Therefore, the main aim of this study was the preparation of uniform macro-porous cellulose acetate (CA) membranes using the vapor-assisted non-solvent induced phase separation (VNIPS) technique. To accomplish this, a cast polymer solution was placed in a defined humid environment at a specific temperature to create controlled and pre-defined pore sizes. Subsequently, the membrane was immersed in a non-solvent bath to complete the membrane formation process. The effects of various solution and processing conditions (specifically humidity and time) on the membrane structure were systematically examined. The results indicated that both humidity levels and fabrication time had a significant impact on membrane performance. Under specific conditions (a polymer solution with 35 wt% n-butanol, approximately 95% humidity, and an exposure duration of 15 min), the produced membranes exhibited a porous, spongy, and symmetrical structure, with a pure water flux of 24–45 mL/cm² min bar, a mean pore size of 0.2–0.5 µm, and an air-flow rate of 18–38 L/min. Finally, the filtration efficiency of the prepared membranes was compared with that of the commercial Sartorius membranes.</p> Graphical abstract <p></p>