The resurgent navigation project known as the Hidrovia Paraguay-Paraná threatens the integrity of the Pantanal, the world's largest wetland, which is considered a biome of its own. Intensive barge navigation is intended to transport crops (soybean, sugar, corn) and cement, iron and manganese from areas of production in Brazil, Paraguay and Bolivia to the oceanic ports of the Plata River. This short communication assembles the information available on the potential impacts of the planned deepening of the natural channel of the Paraguay River in its ~700 km-long upper section. These river channel alterations would disconnect the river from its floodplain, shorten the inundation period, and shrink the wetland area, resulting in severe degradation of the globally outstanding biological and cultural diversity of the Pantanal. The river sediments are mostly sandy and would require perpetual dredging. The reaches needing the most intensive dredging are those of the highest ecological value, protected as a National Park, UNESCO World Heritage and Biosphere Reserves, and various Indigenous reserves and Ramsar sites. Climate change is projected to increase the occurrence of low water periods. Between 2019 and 2021, navigation was impossible even in the already-deepened reaches of the Paraguay River between Corumbá and Asuncion during long periods of the year. Thus, despite considerable financial and technical efforts, the success of the navigation project is doubtful, whereas enormous environmental, cultural, and social impacts can be anticipated. For these reasons, the Brazilian government had already turned down the project in 2000. We suggest alternative, less impactful modes of transport of commodities, e.g., via railway.