The present study undertakes the research problem on the optimization of production of biodiesel as a renewable energy resource from the transesterification of soybean oil and ethanol. Predictive modelling and surface analysis techniques were applied based on the artificial neural network search algorithm to correlate the yield of ethyl ester and glycerol and the input parameters. The formulated models accurately predicted the yield of the products with a high coefficient of determination. When the reaction time is low, the ester yield decreases with an increase in temperature and the maximum yield of obtained biodiesel at a very low value of time of reaction and temperature. Plots based on parametric and sensitivity analysis reveals that the yield of ethyl ester can be maximized and that of glycerol minimized at an integrated condition with lower ethanol/oil molar ratio, higher temperature value, higher catalyst concentration value, and longer time of reaction. The global sensitivity analysis reveals that the catalyst concentration and temperature of the reaction influence the yield of ethyl ester the most. In addition, an optimal ethyl ester yield of 95% can be achieved at specific input conditions. Moreover, according to the results of global sensitivity analysis, the catalyst concentration is found to be most significant for both the glycerol and ethyl ester yield. © 2020 Sri Krishna Murthy et al.