A statistical design of experiments was used to study the effect of reaction temperature and time on the synthesis of cobalt ferrite nanoparticles by the thermodecomposition method. A factorial experimental design with two central points was used in which the control variables were the time and temperature of the nucleation and growth stages. Transmission electron microscopy, X-ray diffraction, inductively coupled plasma optical emission spectroscopy, and magnetic measurements were used for particle characterization. Cobalt-substituted ferrite nanoparticles with diameters between 9 nm and 13 nm were obtained by varying the nucleation temperature between and , the growth temperature between and , and the time in each stage between 60 min and 120 min. Statistical analysis showed that only the temperatures had an influence on the final particle size. The analysis of variance indicates that increase in the nucleation temperature resulted in decreased particle size, whereas the increase in temperature in the growth stage resulted in an increase in particle size. Additionally, statistical analysis showed that the growth temperature had an effect on Fe/Co ratio. An increase in the growth temperature produces a decrease in the Fe/Co ratio. Finally, a statistically significant correlation was found between particle diameter and saturation magnetization at 5 K and 300 K. No correlation was found between diameter and other magnetic properties.