We develop rare-event simulation methodology for the analysis of loss events in a manyserver loss system under quality-driven regime, focusing on the steady-state loss probability (i.e. fraction of lost customers over arrivals) and the behavior of the whole system leading to loss events. The analysis of these events requires working with the full measure-valued process describing the system. This is the first algorithm that is shown to be asymptotically optimal, in the rare-event simulation context, under the setting of many-server queues involving a full measure-valued descriptor.While there is vast literature on rare-event simulation algorithms for queues with fixed number of servers, few algorithms exist for queueing systems with many servers. In systems with single or a fixed number of servers, random walk representations are often used to analyze associated rare events (see for example Siegmund (1976), Asmussen (1985), Anantharam (1988), Sadowsky (1991) and Heidelberger (1995)). The difficulty in these types of systems arises from the boundary behavior induced by the positivity constraints inherent to queueing systems. Many-server systems are, in some sense, less sensitive to boundary behavior (as we shall demonstrate in the basic development of our ideas) but instead the challenge in their rare-event analysis lies on the fact that the system description is typically infinite dimensional (measure-valued). One of the goals of this paper, broadly speaking, is to propose methodology and techniques that we believe are applicable to a wide range of rare-event problems involving many-server systems. In particular, we will demonstrate how measure-valued description is both necessary and useful for efficient simulation. This arises primarily from the intimate relation between the steady-state large deviations behavior and the measure-valued diffusion approximation of many-server systems. As far as we know, the algorithm proposed in this paper is the first provably asymptotically optimal algorithm (in a sense that we will explain shortly) that involves such measure-valued descriptor in the rare-event simulation literature.In order to illustrate our ideas we focus on the problem of estimating the steady-state loss probability in many-server loss systems. We consider a system with general i.i.d. interarrival times and service times (both under suitable tail conditions). The system has s servers and no waiting room. If a customer arrives and finds a server empty, he immediately starts service occupying a server. If the customer finds all the servers busy, he leaves the system immediately and the system incurs a "loss". The steady-state loss probability (i.e. the long term proportion of customers that are lost) is rare if the traffic intensity (arrival rate into the system / total service rate) is less than one and the number of servers is large. This is precisely the asymptotic environment that we consider.Related large deviations and simulation results include the work of Glynn (1995), who developed large deviations as...