The effect of high hydrostatic pressure (HHP) processing at 250 and 450 MPa for 10 min combined with the lactoperoxidase system (LPS) on the inactivation of Listeria monocytogenes H66a and the characteristics of cold-smoked salmon during 35 d at 5°C were investigated. A synergistic antimicrobial effect of 450 MPa and LPS against L. monocytogenes was registered, preventing the pathogen recovery. Biogenic amine formation was avoided. Lightness (L*) values increased by HHP and LPS treatments applied individually or in combination, resulting in a brighter and less transparent appearance of smoked salmon. Redness (a*) and yellowness (b*) were also affected. Hardness and shear strength increased with HHP processing and LPS treatments. HHP at 450 MPa for 10 min in combination with the LPS added to smoked salmon might be used as a hurdle technology approach against L. monocytogenes, increasing the safety and the shelf-life during refrigerated storage. Industrial relevance Antimicrobial activity against L. monocytogenes of high pressure treatments in combination with a biopreservative, the lactoperoxidase system in refrigerated cold-smoked salmon is presented. Color and texture of cold-smoked salmon were affected, whereas the safety and shelf-life of the product were improved. © 2012 Elsevier Ltd.