The aim of this study was to determine the feasibility of using high pressure CO 2 for sterilization of Ginseng powder, as an alternative method to conventional techniques such as g-irradiation and ethylene oxide. The Ginseng sample used in this study was originally contaminated with fungi and 5 ร 10 7 bacteria/g that was not suitable for oral use. This is the first time that high pressure CO 2 has been used for the sterilization of herbal medicine to decrease the total aerobic microbial count (TAMC) and fungi. The effect of the process duration, operating pressure, temperature, and amount of additives on the sterilization efficiency of high pressure CO 2 were investigated. The process duration was varied over 15 h; the pressure between 100 and 200 bar and the temperature between 25 and 758C. A 2.67-log reduction of bacteria in the Ginseng sample was achieved after long treatment time of 15 h at 608C and 100 bar, when using neat carbon dioxide. However, the addition of a small quantity of water/ethanol/H 2 O 2 mixture, as low as 0.02 mL of each additive/g Ginseng powder, was sufficient for complete inactivation of fungi within 6 h at 608C and 100 bar. At these conditions the bacterial count was decreased from 5 ร 10 7 to 2.0 ร 10 3 TAMC/g complying with the TGA standard for orally ingested products. A 4.3 log reduction in bacteria was achieved at 150 bar and 308C, decreasing the TAMC in Ginseng sample to 2,000, below the allowable limit. However, fungi still remained in the sample. The complete inactivation of both bacteria and fungi was achieved within 2 h at 308C and 170 bar using 0.1 mL of each additive/g Ginseng. Microbial inactivation at this low temperature opens an avenue for the sterilization of many thermally labile pharmaceutical and food products that may involve sensitive compounds to g-radiation and chemically reactive antiseptic agents.