Droplet formation in two-phase flow inside minichannels, has been the subject of many studies in recent years. In this work, the process of droplet formation in a co-flowing minichannel has been investigated using the volume of fluid method and the influence of effective parameters such as dispersed phase velocity continuous phase viscosity, interfacial tension, contact angle and dispersed density has been investigated. When the velocity reaches 0.013 m/s the flow regime changes from dripping to jetting. The accuracy of the simulation results was confirmed by comparing against laboratory data. The error is about 5% for droplet size and about 4% for sphericity. A Box-Behnken statical model was developed to study the interaction of parameters and to optimize the process of droplet formation in co-flowing minichannel. At the optimum conditions, the droplet size was measured as 2.34 mm, and the sphericity was calculated as 0.94. Using the analysis of variance and by calculating the p-value, the significant system parameters were determined. It is worth noting that an accurate statistical model can prevent lengthy and costly CFD simulations.