This study reports results of an entire green methodology combining bioreduction by baker's yeast supported cells and a medium formed by glycerol and scCO(2) to a beta-ketoester biotransformation. Fermented cells of Saccharomyces cerevisiae, immobilized in calcium alginate beads, were chosen to catalyze ethyl acetoacetate reduction in a biphasic system of scCO(2) and glycerol 20% (vol/vol) (T = 45 degrees C and P = 100 bar). The bioreduction was also carried out at normal conditions (T = 45 degrees C and P = 0.92 bar) in n-heptane and glycerol 20% (vol/vol). Using scCO(2)/glycerol the reaction reached 77% of conversion in 6 h, and the enantiopure (S)-ethyl-3-hydroxybutyrate (enantiomeric excess > 99%) was observed as the unique product. The same reaction under normal conditions led to only 12% conversion in 6 h. The approach evaluated in this study showed a great potential to be employed as a greener alternative to conventional bioreduction process.