The safety and security of liquefied natural gas (LNG) facilities has prompted the need for continued study of LNG mitigation systems. Water-spray curtains are widely recognized as an effective measure for dispersing LNG vapor clouds (Martinsen et al. Hydrocarbon Process. 1977, 56, 260-267). Currently, there are no engineering guidelines available for water-curtain applications in the LNG industry because of a lack of understanding of the complex interactions between the LNG vapor cloud and water droplets. This work applies computational fluid dynamics (CFD) modeling to investigate the dominant mechanisms observed in the forced dispersion of LNG vapor using upward-oriented full-cone spray nozzles. An Eulerian-Lagrangian approach was used for the continuous and discrete phases to simulate the energy and momentum exchange between the two phases. Discussed are the physical parameters that are essential inputs to the CFD simulation of the water spray-LNG system. The prediction results were also validated with the Mary Kay O'Connor Process Safety Center's LNG outdoor experimental data collected in March 2009 at the Brayton Fire Training Field. On the basis of these findings, dominant mechanisms that govern the effectiveness of water spray in the forced dispersion of LNG vapor clouds are discussed.