The increasing production demands on aquaculture [1] combined with the effects of climate change on marine ecosystems [2] are primary forces driving the emergence of marine opportunistic pathogens belonging to the Vibrio genus, often carrying multidrug resistance, and source of outbreaks of disease in both seafood and humans [3,4]. The use of phages, viral predators of bacteria, could offer new ‘ecological’ solutions to pathogen management [5]. However, bacteria and phages have co-evolved for eons and co-exist in the environment with complex co-adaptation dynamics that impact the efficacy of phages as antimicrobials [6]. Key aspects of these interactions have not yet been fully explored for Vibrio spp. and their phages limiting applicability. Our current study aims to define the link between diversity of target Vibrio spp. isolates and their susceptibility to phage infection. Five phages were isolated against a V. alginolyticus strain (V29) and their lytic activity tested by co-incubation in marine media with the V29 host and other Vibrio spp. isolates (n=20) from Australia and Southeast Asia. Lytic activity was measured as bacterial growth suppression by plaque assays in solid media and by absorbance in liquid. All five phages produced robust lysis alone and in combination against their isolation host. Three of them (P1.1, P1.5 and Fc) also showed cross-reactivity and synergistic effect on clearance of other V. alginolyticus and V. harveyi isolates but with low reproducibility as infection kinetics were heavily influenced by the growth stage and density of the bacteria at the time of phage inoculation. This work provides evidence of lytic phages with strong antibacterial action but shows that phage killing activity is less predictable than in other Gram-negative species.