The aim of this work was to obtain uniform and well-dispersed spherical silver nanoparticles using statistical design-of-experiment methods. We performed the experiments using 2 k fractional factorial designs with respect to key factors of a general chemical reduction method. The nanoparticles prepared were characterized by SEM, TEM and UV-visible absorbance for particle size, distribution, aggregation and anisotropy. The data obtained were analyzed and optimized using a statistical software, Minitab. The design-of-experiment methods using quantified data enabled us to determine key factors and appreciate interactions between factors. The measured properties of nanoparticles were dominated not only by individual one or two main factors but also by interactions between factors. The appropriate combination of the factors produced small, narrow-distributed and non-aggregated silver nanoparticles of about 30 nm with approximately 10% standard deviation.