Aims: To evaluate host range and lytic capability of four bacteriophages (rV5, wV7, wV8 and wV11) against Escherichia coli O157:H7 (STEC O157: H7) from cattle and humans. Methods and Results: Four hundred and twenty-two STEC O157: H7 isolates (297 bovine; 125 human) were obtained in Alberta, Canada. The four phages were serially diluted and incubated for 5 h with overnight cultures of STEC O157: H7 to estimate their multiplicity of infection (MOI). All bovine STEC O157: H7 were subjected to pulsed-field gel electrophoresis (PFGE) and phage typing (PT). Phage wV7 lysed all human and bovine isolates irrespective of PFGE genotype or PT phenotype and exhibited the lowest MOI (0.004-0.006, P < 0 0001) of all phages. Phages rV5 and wV11 exhibited a lower MOI (0.002-004, P < 0 0001) than did phage wV8 (25-29) and they had a narrower host range than wV7 or wV8. Phages rV5, wV11 and wV8 lysed 342 (81.0%), 321 (76.1%) and 407 (96.4%), respectively, of the 422 isolates. Susceptibility of bovine STEC O157: H7 to rV5, w11 and wV8 was influenced by PFGE genotype and/or PT phenotype. Conclusions: Phages exhibited activity against the majority of bovine and human STEC O157: H7 isolates. PFGE genotype and/or PT phenotype of the host- target influenced their vulnerability to phage attack. Susceptibility of bovine STEC O157: H7 to phage may also differ among farms. Both lytic capability and host range should be considered in the selection of therapeutic phage for on-farm control of STEC O157: H7. Significance and Impact of the Study: The present work indicates that a four-phage cocktail should be equally effective at mitigating STEC O157: H7 isolates both of bovine and of human origin. Given that some STEC O157: H7 exhibited resistance to some but not all phages, a phage cocktail is the logical approach to efficacious on-farm therapy.