In our effort to search for effective carbonyl reductases, the activity and enantioselectivity of a carbonyl reductase from Sporobolomyces salmonicolor have been evaluated toward the reduction of a variety of ketones. This carbonyl reductase (SSCR) reduces a broad spectrum of ketones including aliphatic and aromatic ketones, as well as α- and β-ketoesters. Among these substrates, SSCR shows highest activity for the reduction of α-ketoesters. Aromatic α-ketoesters are reduced to (S)-α-hydroxy esters, while (R)-enantiomers are obtained from the reduction of aliphatic counterparts. This interesting observation is consistent with enzyme-substrate docking studies, which show that hydride transfer occurs at the different faces of carbonyl group for aromatic and aliphatic α-ketoesters. It is worthy to note that sterically bulky ketone substrates, such as 2′-methoxyacetophenone, 1-adamantyl methyl ketone, ethyl 4,4-dimethyl-3-oxopentanoate and ethyl 3,3-dimethyl-2-oxobutanoate, are reduced to the corresponding alcohols with excellent optical purity. Thus, SSCR possesses an unusually broad substrate specificity and is especially useful for the reduction of ketones with sterically bulky substituents.