Riverine cetaceans are threatened globally by increasing anthropogenic impacts, and the Yangtze river dolphin Lipotes vexillifer is already extinct. The Amazon river dolphin Inia geoffrensis is widely distributed, but is categorized as Endangered on the IUCN Red List. Drowning in gillnets and being hunted for fish bait are probably the main causes of its decline. A long-term (25-year) study of the biology and ecology of I. geoffrensis in and near the Mamirauá Reserve in Amazonas state, Brazil, has produced estimates of survival and reproductive rates based on the individual recognition of > 650 animals. Concurrently, monthly standardized counts of dolphins along a fixed transect in the Reserve over 22 years demonstrated a sustained, profound decline. In this study we tested whether the measured rate of population decline is consistent with population parameters estimated from independent data, using population viability analysis. With the known parameters as input, programme Vortex predicted population extinction in all scenarios and a 95% loss of dolphins within 50 years. With default parameters, the model predicted a 5.5% annual decline, which is consistent with that observed. We conclude that the Amazon river dolphin population is in severe decline because of human pressures, even in one of the better protected parts of its range. Unless the accidental and deliberate killing of this species is rapidly reduced, it is highly likely that the Amazon river dolphin will follow its Yangtze counterpart to extinction.