The efficacy of a flow-through depuration system in eliminating the human pathogen Vibrio vulnificus from eastern oysters ( Crassostrea virginica ) collected from the North Gulf of Mexico coast was evaluated in this study. Depuration experiments were conducted with artificially inoculated oysters using laboratory-grown strains of V. vulnificus as well as with naturally contaminated oysters. Determination of V. vulnificus numbers in oyster tissues was conducted at 0, 1, 2, 3 and 6 days of depuration. Results showed that the depuration of V vulnificus is possible using a flow-through system. Numbers of V. vulnificus in laboratory-inoculated oysters were reduced from >100,000 Most Probable Number (MPN)/g of oyster tissue to 23 MPN/g after six days of depuration. As expected depuration results of naturally contaminated oysters were more variable. Depuration at low temperature (15°C) had very little success in reducing the numbers of V. vulnificus in oyster tissues. On the contrary, when flow rate was increased from 11 L/m to 68 L/m, numbers of V. vulnificus in oysters were reduced from a starting concentration of 110,000 MPN/g to 3 MPN/g in six days. Nevertheless, a high-flow rate was not enough to eliminate V. vulnificus from oysters consistently. Vibrio vulnificus was effectively eliminated from oysters only when incoming water salinity was higher than 30 parts per thousand (ppt). Depuration did not select for pathogenic V. vulnificus strains. Pre- and post depuration V. vulnificus isolates contained similar proportions of the proposed more virulent type.