Invasive species policies are often directed at pathways of introduction, yet few analyses have examined risk at the pathway level. We synthesize the best available economic and ecological information surrounding International Standards for Phytosanitary Measures No 15 (ISPM15), a pathway-level international phytosanitary policy for treatment of wood packaging material. We highlight temporal factors for calculation of net benefits, emphasizing that while we cannot stop invasions, even delaying new arrivals results in substantial economic benefits. We show that policy implementation, although costly and yielding only moderate protection, can generate >US$11 billion in cumulative net benefits by 2050, averting the introduction of more pests than currently exist in the US. We also discuss the relative importance of different sources of scientific uncertainty and identify the most crucial data needs. This is the first pathway-level economic risk analysis assessing the current scientific evidence for the net benefits of a phytosanitary policy.