Canal Emilio Mitre is a navigation channel that runs through the Rio de la Plata estuary in South America. It grants access to the second largest inland waterway system in South America, covering (parts of) Argentina, Uruguay, Brazil, Paraguay and Bolivia. The channel is a main bottleneck for navigation for two reasons; the channel has a continuous need for maintenance dredging and it is only navigable during a tidal window. Furthermore, the dredging effort shows high interannual variability, resulting in risks for the contractor and users. The current study identifies the dredging effort and strategy, and a conceptual model is made of what physical processes force the sedimentation. The IPCC reports are used to identify the effect of climate change and variability on the drivers of the sedimentation. The interannual variability is shown to be linked to climate variability, due to the ENSO phenomena. The drainage basin of the Rio Parana is affected by an increase in precipitation and sediment input during El Nino events as a result of the teleconnections of ENSO. A depth-averaged numerical model (Delft3D) is set-up to address the effect of climate, deepening and wind scenarios on the dredging effort and its variability. The numerical model was validated by comparing the reported dredged volumes in the system to the simulated sedimentation. Overall, the sedimentation in the system is found to be sensitive to highly energetic events due to a redistribution of the fine sediments over the estuary. The acquired knowledge on the physical processes of the system in combination with the outcomes of the scenarios are used to make recommendations on the future dredging strategy to reduce the risk due to variability. This study highlights the importance of taking into account the risks and chances due to climate variability in dredging projects in regions affected by teleconnections with a duration of around 10 years.