The aim of this work was to evaluate the synergistic effect of combined treatment with high hydrostatic pressure (HHP) and an aqueous extract of Punica granatum (pomegranate) peels on the survival of Shiga toxin-producing Escherichia coli (STEC). Our results showed that HHP (250 MPa, 60 min, 25 ºC) reduced the STEC bacterial load in milk and tryptic soy broth culture medium by about 2.5 and 3.5 logs, respectively. Under these conditions, HHP did not alter the cytotoxicity of Shiga toxins in Vero and human umbilical vein endothelial cells. Treatment with up to 30 mg of pomegranate extract/mL caused negligible inactivation, but a combination of HHP and pomegranate extract (3 mg/mL) produced bacterial inactivation from 109 CFU/mL to undetectable levels of viable bacteria. These findings suggest that a combination of HHP and pomegranate extract may be potentially effective in bacterial inactivation during food processing, particularly in the elimination of important foodborne pathogens such as STEC. a