The cold box heat exchangers are used in petrochemical and gas refinery industries. Here, an industrial complex cold box equipped with a number of plate-fins is simulated by computational fluid dynamics. The model predicts the outlet vapor fraction, pressure drop, and outlet temperature with average absolute relative deviations of 0.17%, 3.3%, and 12.89% for all streams, respectively. The influence of obstruction in streams B and C on the computational fluid dynamics results are studied. When stream B or C is blocked, the remaining open streams experience an increase in pressure drop, temperature, and vapor fraction, which negatively affects the heat exchanger's performance over a long time. Finally, the computational fluid dynamics results of the cold box are compared with those of commercial software Aspen-EDR. Even though Aspen-EDR predicts an acceptable mean temperature and vapor fraction (phase change) along channels, it calculates pressure drop incorrectly. So, Aspen-EDR, computationally efficient software, can be used for modeling of mean temperature and phase change of flow in an industrial multi-stream cold box.