Biodiesel has limitations regarding its performance in cold weather. Therefore, the fuel industry requires the production of biodiesel additives from renewable, non-edible sources, at a viable price, and ethyl levulinate is a promising candidate. In this investigation, a reactive distillation column is proposed and optimized to operate at high temperature to promote the uncatalyzed esterification of levulinic acid to ethyl levulinate. A central composite design was applied to determine the optimized operating conditions, and the results were analyzed based on response surfaces. The results showed that optimized reactive distillation column provides a production cost of $0.247 per kg of ethyl levulinate, including ethanol, capital and operational expenditures, a value 2.3% lower than that of an equivalent process comprised of a reactor followed by conventional distillation.