The effect of sonification on D-fructose hydrogenation over several heterogeneous catalysts was investigated. The reaction rate and selectivity were studied at different temperatures, pressures, and ultrasonic power inputs. The ultrasonic effects were clearly catalyst dependent. The sonification during the hydrogenation reaction significantly enhanced reaction rate over Cu/ SiO2. In the case of Raney-Ni, just moderate improvements of reaction rates were observed under ultrasound and a slight decrease of catalyst activity by sonification was obtained over Cu/ZnO/Al2O3. Although the choice of catalyst significantly influenced selectivity, no positive influence of acoustic irradiation on selectivity was achieved. The influence of pressure and temperature over Raney-Ni type catalyst was studied under sonification as well. High pressures and temperatures brought just moderate enhancements of reaction rates, while the variation of nominal ultrasonic power input significantly affected the catalyst activity. A catalyst deactivation study was conducted by recycling the catalyst. Acoustic irradiation significantly prevented catalyst deactivation compared to experiments in silent conditions. The effect of ultrasound on catalyst surface was confirmed by means of scanning electron microscopy (SEM).