Direct synthesis of ethyl acetate from ethanol is investigated over several copper catalysts. We clarified the role of additive metal oxides such as ZrO2, ZnO and Al2O3. An additive ZrO2 gives ester-formation activity to the pure copper catalyst. ZnO suppresses the formation of undesirable products such as methyl ethyl ketone (MEK) under the co-existence of ZrO2. Al2O3 enhances not only the conversion of ethanol but also the catalytic activity for the side reaction of aldol addition of acetaldehyde. Ethanol is converted into ethyl acetate with high selectivity over Cu-ZnO-ZrO2-Al2O3 catalyst, together with low selectivity to methyl ethyl ketone. Then we investigated the influence of copper content in the quaternary copper catalysts containing ZrO2, ZnO and Al2O3 on the catalytic performance. The ethyl acetate production ability of catalyst is roughly proportional to the Cu surface area of the Cu-ZnO-ZrO2-Al2O3 catalyst. The highest ethanol conversion, the highest ethyl acetate selectivity, and the highest space-time yield of ethyl acetate were achieved at Cu content of 70 mol%.