The eradication of newly detected alien plant species is often prescribed, but rarely successful. Eradication programs fail for many reasons, however, for eradication to remain a cost-efficient management option it is clear that good decisions must be made at the outset. Here we re-frame the project prioritization protocol (PPP), a tool widely used in conservation biology, for use with the metrics typically used by a biosecurity agency. We then use existing methods to estimate the cost-efficiency of eradicating 50 hypothetical species incursions and compare the reduction in weed risk achieved by allocating resources using the PPP framework with the allocation based on risk ranking. By allocating resources to plant eradication programs using the PPP our analysis indicated that it is possible to improve the return on public expenditure by 25% compared to investing based solely on weed risk assessment scores. We also demonstrate how the cost-efficiency of the overall portfolio is influenced by the choice of planning horizon; including the decline in overall portfolio performance that arises when attempting to eradicate individual species too quickly. Finally, we discuss the logistical benefits to a management agency that arise from the use of a generic overarching framework such as the PPP. We believe that the PPP has considerable potential for use in biosecurity and can help focus attention on those species where management can make the biggest difference.