Recently, there has been increasing interest in simulating all aspects of the seismic risk problem, from the source mechanism to the propagation of seismic waves to nonlinear time-history analysis of structural response and finally to building damage and repair costs. This study presents a framework for performing truly "end-to-end" simulation. A recent region-wide study of tall steel-frame building response to a Mw 7.9 scenario earthquake on the southern portion of the San Andreas Fault is extended to consider economic losses. In that study a source mechanism model and a velocity model, in conjunction with a finite-element model of Southern California, were used to calculate ground motions at 636 sites throughout the San Fernando and Los Angeles basins. At each site, time history analyses of a nonlinear deteriorating structural model of an 18-story steel moment-resisting frame building were performed, using both a pre-Northridge earthquake design (with welds at the moment-resisting connections that are susceptible to fracture) and a modern code (UBC 1997) design. This work uses the simulation results to estimate losses by applying the MDLA (Matlab Damage and Loss Analysis) toolbox, developed to implement the PEER loss-estimation methodology. The toolbox includes damage prediction and repair cost estimation for structural and non-structural components and allows for the computation of the mean and variance of building repair costs conditional on engineering demand parameters (i. e. inter-story drift ratios and peak floor accelerations). Here, it is modified to treat steel-frame high-rises, including aspects such as mechanical, electrical and plumbing systems, traction elevators, and the possibility of irreparable structural damage. Contour plots of conditional mean losses are generated for the San Fernando and the Los Angeles basins for the pre-Northridge and modern code designed buildings, allowing for comparison of the economic effects of the updated code for the scenario event. In principle, by simulating multiple seismic events, consistent with the probabilistic seismic hazard for a building site, the same basic approach could be used to quantify the uncertain losses from future earthquakes.