One-pot synthesis of R-1-phenylethyl acetate starting from acetophenone hydrogenation was studied over supported palladium catalysts in combination with an immobilized lipase. Ethyl acetate was used as an acyl donor and the experiments were carried out under 1 bar hydrogen at 70 °C. In this work, the effect of support acidity was systematically investigated by using two mesoporous Pd-H-MCM-41 and Pd-Si-MCM-41 catalysts as hydrogenation catalysts. Furthermore their performance was compared with the performances of Pd-SiO2 and Pd-Al2O3. The catalysts acidity was determined by pyridine adsorption while the metal crystallite sizes were measured by XRD technique. The initial hydrogenation rates of acetophonene decreased with increasing Pd crystallite sizes. Initially both R- and S-1-phenylethanol were formed with the same rates. After prolonged reaction times activities of both hydrogenation catalyst and lipase declined. The former catalyst deactivated due to formation of acetic acid via deacylation reaction, whereas ethanol formed as a stoichiometric product in acylation decreased the lipase activity. The formation of ethylbenzene via dehydration of an intermediate alcohol, (R,S)-1-phenylethanol was enhanced by acidic catalysts. The most selective catalyst for one-pot synthesis of R-1-phenylethylacetate was a slightly acidic Pd-Al2O3 in combination with lipase. A reaction network was proposed based on the kinetic data.