Many studies have compared corn-based ethanol to cellulosic ethanol on a per unit basis and have generally concluded that cellulosic ethanol will result in fewer environmental consequences, including nitrate (NO3(-)) output. This study takes a system-wide approach in considering the NO3(-) output and the relative areal extent of hypoxia in the Northern Gulf of Mexico (NGOM) due to the introduction of additional crops for biofuel production. We stochastically estimate NO3(-) loading to the NGOM and use these results to approximate the areal extent of hypoxia for scenarios that meet the Energy Independence and Security Act of 2007's biofuel goals for 2015 and 2022. Crops for ethanol include corn, corn stover, and switchgrass; all biodiesel is assumed to be from soybeans. Our results indicate that moving from corn to cellulosics for ethanol production may result in a 20-percent decrease (based on mean values) in NO3(-) output from the Mississippi and Atchafalaya River Basin (MARB). This decrease will not meet the EPA target for hypoxic zone reduction. An aggressive nutrient management strategy will be needed to reach the 5000 km2 areal extent of hypoxia in the NGOM goal set forth by the Mississippi River/Gulf of Mexico Watershed Nutrient Task Force even in the absence of biofuels, given current production to meet food, feed, and other industrial needs.