AbstractA modified acetone process for the preparation of aqueous polyurethane (PU) dispersion is investigated. PU dispersions were prepared by polyaddition of isophorone diisocyanate (IPDI) to poly(tetramethylene ether glycol) (PTMG) and dimethylolpropionic acid (DMPA), followed by neutralization of pendant COOH groups with triethylamine (TEA). The resulting prepolymer chain was then extended through reaction with an ethylenediamine (EDA) derivative bearing sulfonate groups. The effect of such preparation conditions as catalyst (dibutyltin dilaurate, DBTDL) concentration, the acetone/PU ratio, phase‐inversion temperature, agitation rate, and water‐addition rate on the average particle size of aqueous PU anionomer dispersions is systematically studied using fractional factorial design and response surface methodology. Fractional factorial analysis indicates that the effects of the acetone/PU ratio, phase‐inversion temperature, water‐addition rate as well as the two factor interactions of DBTDL concentration and phase‐inversion temperature, of the acetone/PU ratio and phase‐inversion temperature, and of acetone/PU ratio and agitation rate are the key variables influencing average particle size of PU dispersions. Empirical models for average particle size are fitted and plotted using central composite experimental design as contour diagrams in order to facilitate examination of the average particle size results. The results show that for a 100 g PU anionomer containing 0.311 wt % COOH and 1.51 wt % SO3H groups, a minimum number‐average particle size of the dispersion ∼ 25 nm can be obtained under an acetone/PU ratio, water‐addition rate, phase‐inversion temperature, catalyst concentration, and agitation rate of 3.65, 2 mL/min, 50°C, 150 ppm and 350 rpm, respectively.