An enantioselective esterification process was developed for the direct synthesis of (S)-ibuprofen ester prodrug from racemic ibuprofen by using 2-N-morpholinoethanol as an acyl acceptor and Candida rugosa lipase as the biocatalyst in organic solvents. By selecting cyclohexane as the best reaction medium, the apparent fit of the specific initial rate for (S)-ibuprofen and time-course conversions for both enantiomers supported the proposed reversible ping-pong Bi Bi enzymatic mechanism with a competitive inhibition by the alcohol. Moreover, the recovery and racemization of the remaining (R)-ibuprofen, as well as an investigation of the present kinetic model applied to high substrate concentrations, were reported.