An l-Proline (l-Pro)-catalyzed aldol reaction of acetone and p-nitrobenzaldehyde (pNBA) occurs in organic solvents such as DMSO, while the presence of excess water inhibits the reaction. Herein, the reaction was carried out in water, in the presence of liposomes. Most liposomes assisted in the conversion of the substrates (conv. >90%). We conclude that the hydrophobic environment of the liposome can be utilized as a reaction medium for this organocatalytic reaction. Although the l-Pro-catalyzed aldol reaction in dimethyl sulfoxide (DMSO) resulted in a high enantiomeric excess of R product (e.e. >70%), the reactions on liposome membranes resulted in e.e. values of 1%.