Biocatalytic synthesis of ethylhexyl palmitate and ethylhexyl stearate as natural alternatives of cyclomethicone has been studied. In this work the esters have been obtained with two commercial enzymes: Novozym (R) 435 and Novozym (R) 40086 in a "solvent free" system. Operational conditions have been optimized using experimental design and response surface methodology. In the optimum reaction conditions conversion values were higher than 85% in one hour in all the cases. Operation in vacuum reactors with constant N-2 bubbling improved the obtained results since it favours water removal and, in consequence, the shifting reaction equilibrium in the way of the synthesis. Besides, Candida antarctica lipase Novozym (R) 435 was the most effective, reaching a conversion value of 98% in 45 min. However, cost study revealed that the process is cheaper when using Novozym (R) 40086 in open-air reactors.