The antimicrobial effect of high hydrostatic pressure (HHP) processing combined with reuterin, lactoperoxydase system (LPS) and lactoferrin (LF) on the survival of Listeria monocytogenes, Salmonella enterica subsp. enterica serovar Enteritidis and Escherichia coli O157:H7 in sliced cooked ham stored under strict refrigeration temperature (4 °C) and mild temperature abuse conditions (10 °C) was investigated. One day after treatment, L. monocytogenes counts in HHP at 450 MPa for 5 min were 0.8 log units lower, but a recovery was observed with counts not significantly different to those observed in control after 35 d. S. Enteritidis and E. coli O157:H7 levels were reduced around 5 log cfu/g by the pressure treatment (450 MPa/5 min) and the numbers of these pathogens did not increase significantly during the 35 d of storage at 4 °C. The individual application of reuterin and LPS influenced the survival of the three pathogens studied, extending the lag phase of L. monocytogenes and diminishing S. Enteritidis and E. coli levels throughout storage, whereas no effect was recorded when LF was added. When reuterin or LPS were applied in combination with HHP there was a synergistic antimicrobial effect against L. monocytogenes, avoiding at 4 °C the recovery observed with individual treatments. These combined treatments also kept the levels of S. Enteritidis and E. coli O157:H7 below the detection limit (<1 log unit) in cooked ham stored at 4 and 10 °C during 35 d. The results obtained in the present work suggest that HHP at 450 MPa for 5 min in combination with LPS or reuterin would be useful as a hurdle technology approach against L. monocytogenes, S. Enteritidis and E. coli O157:H7 in cooked ham.