In this investigation, four scenarios were used to quantify the balance between the benefits of levees for flood protection and their potential to increase flood risk using Hazards U.S. Multi-Hazard flood-loss software and hydraulic modeling of the Middle Mississippi River (MMR). The goals of this study were (1) to quantify the flood exposure under different flood-control configurations and (2) to assess the relative contributions of various engineered structures and flood-loss strategies to potential flood losses. Removing all the flood-control structures along the MMR, without buyouts or other mitigation, reduced the average flood stages between 2.3 m (100-year flood) and 2.5 m (500-year), but increased the potential flood losses by $4.3-6.7 billion. Removing the agricultural levees downstream of St. Louis decreased the flood stages through the metro region by *1.0 m for the 100-and 500-year events; flood losses, without buyouts or other mitigation, were increased by $155 million for the 100-year flood, but were decreased by $109 million for the 500-year flood. Thus, agricultural levees along the MMR protect against small-to medium-size floods (up to the *100-year flood level) but cause more damage than they prevent during large floods such as the 500-year flood. Buyout costs for the all the buildings within the 500-year floodplain downstream of urban flood-control structures near St. Louis are *40% less than the cost of repairing the buildings damaged by the 500-year flood. This suggests large-scale buyouts could be the most cost-effective option for flood loss mitigation for properties currently protected by agricultural levees.