Context: Recent studies have shown that the sensitivity of wild house mice to zinc phosphide (ZnP) in Australia is significantly lower than previously assumed, which may account for the reported variability in efficacy of ZnP baits used for broadacre control of house mice in grain-growing regions. Under laboratory conditions ZnP-coated grains with a new higher dose (50 g ZnP/kg grain) were readily consumed but the efficacy of using grains with this higher dose under natural field conditions has not been tested. Aims: To test whether the newly derived ZnP50 (50 g ZnP/kg grain) was more effective under field conditions than the currently registered ZnP25 (25 g ZnP/kg grain) in reducing populations of house mice during a mouse population irruption. Methods: We used a before-after-control-impact (BACI) design to assess changes in mouse population size under different baiting treatments in a replicated field trial. We assessed changes in mouse abundance in recently sown paddocks with either ZnP50 (n = 3) or ZnP25 (n = 3) compared with unbaited control sites (n = 3). Key results: Baiting with ZnP50 led to a median reduction in mouse numbers of >85%. Our modelling showed that under similar circumstances, using the ZnP50 formulation should deliver >80% reduction in population size most (>90%) of the time. In contrast, the current registered bait (ZnP25) achieved approximately 70% reduction in population size, but with more variable results. We would be confident of getting an 80% reduction in population size only 20% of the time by using the currently registered ZnP25 bait under similar field conditions. Conclusions: Consistent with laboratory studies, this study demonstrated the higher probability of achieving a consistently high kill rate under field conditions with the new ZnP50 bait compared with the currently registered formulation (ZnP25). Implications: By using the new ZnP50 bait, farmers are far more likely to get good kill rates, thereby reducing the need for repeated baiting (which is costly and generally ineffective at protecting newly sown crops). Using the new bait should result in lower control costs for farmers and fewer toxic grains being spread to control mice.