A large region of low-dissolved-oxygen bottom waters (hypoxia) forms nearly every summer in the northern Gulf of Mexico because of nutrient inputs from the Mississippi River Basin and water column stratification. Policymakers developed goals to reduce the area of hypoxic extent because of its ecological, economic, and commercial fisheries impacts. However, the goals remain elusive after 30 y of research and monitoring and 15 y of goal-setting and assessment because there has been little change in river nitrogen concentrations. An intergovernmental Task Force recently extended to 2035 the deadline for achieving the goal of a 5,000-km 2 5-y average hypoxic zone and set an interim load target of a 20% reduction of the spring nitrogen loading from the Mississippi River by 2025 as part of their adaptive management process. The Task Force has asked modelers to reassess the loading reduction required to achieve the 2035 goal and to determine the effect of the 20% interim load reduction. Here, we address both questions using a probabilistic ensemble of four substantially different hypoxia models. Our results indicate that, under typical weather conditions, a 59% reduction in Mississippi River nitrogen load is required to reduce hypoxic area to 5,000 km 2 . The interim goal of a 20% load reduction is expected to produce an 18% reduction in hypoxic area over the long term. However, due to substantial interannual variability, a 25% load reduction is required before there is 95% certainty of observing any hypoxic area reduction between consecutive 5-y assessment periods.ensemble modeling | hypoxia | Gulf of Mexico | nitrogen-loading targets A large region of low-dissolved-oxygen (DO) bottom waters (hypoxia; DO < 2 mg·L −1 ) has formed nearly every summer in the Gulf of Mexico for at least the last three decades (1-3). Hypoxia forms because of respiration of organic matter in bottom waters and a vertically stratified water column restricting reaeration (4-6). Both factors are related to the outflow of freshwater and nutrients from the Mississippi River Basin, which typically peaks in March through May. Nutrients stimulate phytoplankton production, much of which settles in early summer, and bottom water DO (BWDO) is consumed during its decomposition. River outflows create a fresher, warmer surface layer above a colder, saltier bottom layer, limiting the vertical diffusion of DO (2).Policymakers developed hypoxia reduction goals because of ecological, economic, and commercial fisheries impacts (7-10). However, the goals remain elusive after >30 y of research and monitoring (3, 11) and >15 y of assessment and goal-setting (5, 12-16). A Gulf Task Force recently agreed to retain the 5-y moving average goal of a 5,000-km 2 hypoxic zone, but extended the deadline from 2015 to 2035 (17). The timeframe was reset because the 2015 hypoxic zone was 16,760 km 2 and the most recent 5-y average was 14,024 km 2 -greater than the long-term average of 13,751 km 2 (1). Missing the goal was not unexpected because the 5-y average load of late sp...