In the present paper are discussed the optimal experimental conditions for biodegradation of organic content of winery wastewater, using an anoxic hybrid bioreactor. The response surface models are proposed in terms of coded and real variables in order to predict the COD removal efficiency and the specific volumetric capacity of biogas production as the functions of operating variables. Based on both responses the objective function has been developed. The optimal conditions of the experiment have been calculated using Monte Carlo stochastic simulation method and were found to be: HRT*=67.46 h; pH* = 7.37 and dilution coeficient of winery waste waters of d* = 4.08. In optimal point the estimation of COD removal efficiency is approaching 100%. The spatial representations of responses versus independent variables have been drawn.