The stereoselectivity of Baker's yeast reduction of prochiral alpha-oxygenated 2-propanones has been studied by varying the substrate structure. The 1-hydroxy-3-methoxy-3-propanone 1a was reduced to the corresponding alcohol (R)-2a with 88% enantiomeric excess. Replacing the hydroxy group in 1a with phenoxy or benzyloxy (1b and 1c) gave the alcohols (S)-2b and (S)-2c with 53 and 32% ee, respectively. Reduction of the methyl ketone 1d gave the alcohol (S)-2d with 91% ee. Attempts to improve the enantioselectivity of the reduction of 1c by lowering the substrate concentration or addition of selective reductase inhibitors had only small effect on the enantioselectivity.