The recent increase in the applications of ultrasound for benign environmental remediation, chemical and materials synthesis, and biological processes presents an urgent need to optimize the sonochemical process to reduce the cost of operation and make it economically attractive for large-scale applications. This paper reports for the first time the application of the Taguchi statistical method to design experiments and optimize a sonochemical process. The model reaction chosen for study was the sonochemical oxidation of carbon disulfide, and the response measured was the amount of sulfate (i.e., the predominant oxidation product) formed during the ultrasonic irradiations. The effects of the key process parameters (i.e., temperature, ultrasonic intensity, irradiation gas, and frequency) on the sonochemical reaction were studied. A state-of-the-art sonicator capable of supplying ultrasonic energy at four pre-set frequencies (323, 581, 611, and 1300 kHz) and five different power settings (ranging from 13 to 223 W) for each frequency was employed. The gases studied were helium, air, oxygen, argon, and 75% argon/25% oxygen mixtures in the temperature range of 5-50 degrees C. The statistical tool used in the Taguchi method to analyze the data was the analysis of variance (ANOVA), which gave the relative contribution of each of the factors varied to the change in the dependent variable (i.e., sulfate production).