A numerical sedimentation model assessment was conducted to determine the effects of long-term sedimentation processes on the Project Design Flood (PDF) flowline for the Mississippi River. The assessment reach was between Pilots Station, which is located at the end of Southwest Pass in Louisiana, and Cairo, IL, which is located at the confluence of the Ohio River. In addition, the assessment determined the effects of scour and deposition, which occur during the passage of the PDF hydrograph, on maximum water-surface elevations. The HEC-6T numerical sedimentation model was used in this assessment. The assessment identified a long-term degradation trend between Helena, AR, and Cairo, IL, and a long-term aggradation trend between Helena, AR, and Red River Landing, Louisiana. The numerical model was used to evaluate the effects of several driving variables on the long-term sedimentation trends. These variables included the effects of floods, sediment inflow, dikes, historical cutoffs, sea-level rise, and subsidence. The assessment results provide 50-year increases in PDF water-surface elevations attributed to sedimentation in the Mississippi River. These results are to be added to water-surface elevations calculated using an unsteady flow HEC-RAS model that uses current surveys to define the HEC-RAS geometry.