Benzaldehyde lyase is a versatile catalyst for the organic synthesis of enantiopure -hydroxy ketones. In view of poor solubility and stability of many substrates and products and the prospect of downstream processing, supercritical fluids are explored as an alternative solvent in view of residual stability, activity, and selectivity. Four supercritical fluids were investigated: carbon dioxide, fluoroform, ethane, and sulphur hexafluoride. Water activity and enzyme preparation (pH of lyophilisation) showed to be the main influence parameters. Activity increased with increasing water activity but stability decreased. Furthermore, non-carbon dioxide supercritical fluids give better results in view of stability, activity, and enantioselectivity. Suprisingly, the enantioselectivity is heavily influenced by the reaction from almost racemic in sulphur hexafluoride with up to 90% enantiomeric excess.