Hospital as a service provider has an important role in human life, especially for people who are experiencing physical and mental disorders. Various types of diseases and therapies performed in hospitals has made it as one of the producers of hazardous and infectious waste that requires special handling and processing so as not to pollute the water, soil, and air environment. Hospital wastewater treatment was conducted to determine the ability of sonochemical method to reduce level of Chemical Oxygen Demand (COD) and determine the optimum conditions of the parameters used by the design of Response Surface Methodology Box-Behnken. The parameters that affected this process was the concentration of hydrogen peroxide (H 2 O 2), pH, and reaction time. The Waste used was taken from the waste water treatment plant in Zainoel Abidin General Hospital in Banda Aceh with COD value 260.65 ppm. The optimum conditions of this treatment process occured at pH 2, H 2 O 2 concentration 500 ppm, and reaction time 119.98 minutes with reduction of COD was 81.88%.