Enantiocomplementary R- and S-cyanohydrins were synthesized at high ee and yield through the biocatalytic hydrocyanation of a variety of aromatic methyl and ethyl ketones and pyridinecarboxaldehydes. Commercially available hydroxynitrile lyases (HNLs) were used in liquid solution or cross-linked enzyme aggregate (CLEA) forms to catalyze the reactions and produce material with optical purities significantly greater than has been reported previously. Among these processes are the first syntheses of chiral cyanohydrins from substituted derivatives of phenylacetone, benzylacetone and propiophenone. Selection of an optimal solvent system and cyanide source was crucial in improving cyanohydrin stereoselectivity through minimizing background racemic cyanide addition and enzyme-catalyzed racemization of the product. Additionally, both reaction yields and product chiral purity were shown to be influenced by the carbon chain length between ketone and phenyl functional groups, and the type of aromatic substitution present on the starting material.