With the increasing global spread of human noroviral infections and the emergence of highly virulent noroviral strains, novel inactivation methods are needed to control foodborne outbreaks. High pressure homogenization (HPH) is a novel method that can be applied for foodborne virus reduction in fluids being continuously processed. Our objective in the present study was to compare the titer reduction by HPH between feline calicivirus strain F9 (FCV-F9) and murine norovirus 1 (MNV-1) as surrogates for human noroviruses, and MS2 (single-stranded F-RNA coliphage) and somatic coliphage ϕX174 (single-stranded DNA) as indicators of fecal contamination. Duplicate experiments with each virus in phosphate-buffered saline were carried out with homogenization pressures of 0, 100, 200, 250, and 300 MPa, with exposure temperatures of 24, 46, 63, 70, and 75°C, respectively, for <2 s. FCV-F9 was found highly susceptible to HPH treatment pressures of 300 MPa, with a reduction of >4.95 log PFU/ml. Lower pressures of 250, 200, and 100 MPa resulted in reductions of 1.61, 0.60, and 0.18 log PFU/ml of FCV-F9, respectively, while MNV-1 was not reduced at these lower pressures. Coliphage ϕX174 showed no significant reduction at 300 MPa or lower homogenization pressures in comparison with MS2, which did show 3.3-log PFU/ml reduction at 300 MPa. Future studies using juices for industrial application of HPH to determine microbial inactivation with simultaneous retention of sensory and nutritional value of foods are needed.