The degradation of specific iodinated X-ray contrast media (ICM) compounds (viz: diatrizoate, iomeprol, iopromide, and iopamidol) by ultrasound irradiation in aqueous solution, with and without the presence of hydrogen peroxide or ozone, has been studied. Experiments were carried out at a constant ultrasound frequency of 20 kHz, at two power intensity values of 17.6 and 200.1 W cm−2, and at five power densities up to 0.235 W ml−1. Zero-order kinetic rate constants for the ICM degradation by ultrasound alone were calculated under certain sonication conditions. Pyrolysis appeared to contribute approximately 30%, and radical attack 70%, of the overall ICM degradation performance. The effect of ultrasound intensity on compound degradation (at a given power density) was found to play a negligible role, whereas ultrasound power density was found to be a major factor controlling the overall oxidation process under these conditions. The compound degradation by ultrasound alone was relatively minor, but the addition of hydrogen peroxide in the sonication process gave some improvement with a doubling in the degradation performance at the greatest applied peroxide concentration. The combination of gaseous ozone and ultrasound was found to be very effective in degrading ICM compounds and an almost complete compound removal could be achieved.