We present a quantum transport simulation of a 4.6-µm quantum cascade laser (QCL) operating at high power near room temperature. The simulation is based on a rigorous density-matrix-based formalism, in which the evolution of the single-electron density matrix follows a Markovian master equation in the presence of applied electric field and relevant scattering mechanisms. We show that it is important to allow for both position-dependent effective mass and for effective lowering of very thin barriers in order to obtain the band structure and the current-field characteristics comparable to experiment. Our calculations agree well with experiments over a wide range of temperatures. We predict a room-temperature threshold field of 62.5 kV/cm and a characteristic temperature for threshold-current-density variation of T 0 = 199 K. We also calculate electronic in-plane distributions, which are far from thermal, and show that subband electron temperatures can be hundreds to thousands of degrees higher than the heat sink. Finally, we emphasize the role of coherent tunneling current by looking at the size of coherences, the off-diagonal elements of the density matrix. At the design lasing field, efficient injection manifests itself in a large injector/upper lasing level coherence, which underscores the insufficiency of semiclassical techniques to address injection in QCLs.