The achievement and improvement of the economic profitability of an enterprise is the true measure of management efficiency. The return of sales and turnover of the assets of the enterprise are the basic drivers of economic profitability. The purpose of the current research is to evaluate and determine all factors which are drivers of economic profitability of wineries in southern Bulgaria. The DuPont approach is used for evaluation of all drivers of economic profitability. The results of the research show that the return of sales is a key driver which determines the economic profitability of wineries.