Cellulose acetate (CA) flat sheet membranes were fabricated and evaluated in a forward-osmosis process. Effects of CA concentration, coagulation bath temperature, and annealing thermal treatment on both membrane structure and performance were investigated. NaCl rejection of the optimum membrane was determined utilizing a reverse-osmosis setup based on conductivity measurements. Two validated models were obtained by means of response surface methodology based on Box-Behnken design. The optimum operating pressure, temperature, and draw solution concentration were assessed as well.