Abstract This study identified and validated high hydrostatic pressure processing (HPP) for achieving greater than 3.52-log reductions of Vibrio parahaemolyticus in the Pacific oysters (Crassostrea gigas) and determined shelf life of processed oysters stored at 5°C or in ice. Raw Pacific oysters were inoculated with a clinical strain of V. parahaemolyticus 10293 (O1:K56) to levels of 104–5 cells per gram and processed at 293MPa (43K PSI) for 90, 120, 150, 180 and 210s. Populations of V. parahaemolyticus in oysters after processes were analyzed with the 5-tube most probable number (MPN) method. Negative results obtained by the MPN method were confirmed with a multiplex PCR detecting genes encoding thermolabile hemolysin (tl), thermostable direct hemolysin (tdh) and TDH-related hemolysin (trh). A HPP of 293MPa for 120s at groundwater temperature (8±1°C) was identified capable of achieving greater than 3.52-log reductions of V. parahaemolyticus in Pacific oysters. Oysters processed at 293MPa for 120s had a shelf life of 6–8days when stored at 5°C or 16–18days when stored in ice. This HPP can be adopted by the shellfish industry as a post harvest process to eliminate V. parahaemolyticus in raw oysters.