This study focused on the identification of suitable lipase or esterase activity for enantiomeric resolution of (R,S)-naproxen. For an economically viable reaction the enantiomeric ratio (E) should preferably be >100, while maximising the conversion will reduce the mass of material that requires racemisation and recycling. Hence the aim was to find an enzyme that yields (S)-naproxen with an enantiomeric excess of more than 98%, a substrate conversion in excess of 40% of the racemate, and an E of >100. (R,S)-Naproxen ethyl ester (NEE) (50 mg) was used as substrate for enzyme hydrolysis reactions at 37 degreesC for 4 h. Biocatalyst screening was performed in buffered aqueous solvent on a I ml scale. The reactions were stopped with 2 ml MeCN, filtered through cotton wool and analysed by HPLC to determine the percentage m/m and R/S ratio. Eight commercially available enzymes were selected for optimisation of enantioselectivity through statistically designed experiments where the reaction conditions were varied. ChiroCLEC-CR from Altus and ESL001-01 from Diversa provided acceptable enantiomeric excess, but only ChiroCLEC-CR met the specification set for the enantiomeric ratio (E).