This paper presents key parameters that affect numerical modeling of steel frame structures for reliable collapse simulations. The collapse assessment is based on experimental data obtained from a full-scale shaking table collapse test of a 4-story steel moment frame and a blind numerical analysis contest that was organized in parallel with the collapse test. It is shown that (1) there is no clear advantage between three-dimensional (3D) and 2D analyses in the prediction of a sidesway collapse mechanism for buildings with a regular plan view as in the case of study; (2) the assumption of Rayleigh damping leads to better predictions of structural response compared with stiffness proportional damping; and (3) accurate prediction of collapse necessitates that P-Δ effects always be considered in the analysis. It is also proven that accurate simulation of steel component deterioration is a key factor for reliable prediction of collapse behavior. On the basis of a synthesis of experimental and analytical studies, a few collapse mitigation alternatives are investigated. In particular, the effects of the strong-column/weak-beam ratio and exposed base plates on the collapse capacity are assessed. It is notable that a combination of bending strength increase and delay of local buckling in first-story columns is most effective for the enhancement of seismic performance against collapse. © 2013 American Society of Civil Engineers.