The substrate selectivity of Candida antarctica lipase for various carboxylic acids was systematically investigated for their condensation with p-methoxyphenethyl alcohol in acetonitrile. The electron density of a carboxylic carbon and the projection area of an acid molecule were numerical indicators for evaluating the substrate selectivity. Both the electron density and projection area had an influence on the V/K-m value, while only the projection area affected the K value. The presence of conjugation with a carboxyl group in an acid and a branched structure in the non-carboxylic region independently lowered the V/K-m value by an order of 1.