Based on OpenSHA and HAZUS-MH, we present loss estimates for an earthquake rupture on the recently identified Puente Hills blind-thrust fault beneath Los Angeles. Given a range of possible magnitudes and ground motion models, and presuming a full fault rupture, we estimate the total economic loss to be between $82 and $252 billion. This range is not only considerably higher than a previous estimate of $69 billion, but also implies the event would be the costliest disaster in U.S. history. The analysis has also provided the following predictions: 3,000-18,000 fatalities, 142,000-735,000 displaced households, 42,000-211,000 in need of short-term public shelter, and 30,000-99,000 tons of debris generated. Finally, we show that the choice of ground motion model can be more influential than the earthquake magnitude, and that reducing this epistemic uncertainty (e.g., via model improvement and/or rejection) could reduce the uncertainty of the loss estimates by up to a factor of two. We note that a full Puente Hills fault rupture is a rare event (once every ???3,000 years), and that other seismic sources pose significant risk as well. ?? 2005, Earthquake Engineering Research Institute.