Single-phase and two-phase flow distribution in plate-fin heat exchangers and the influence of nonuniform fluid flow distribution on the thermal performance of such heat exchangers were experimentally investigated. The experimental results show that flow maldistribution can be a serious problem in plate-fin heat exchangers because of nonoptimized header configurations. The uneven distribution of two-phase flow in plate-fin heat exchangers is more pronounced than that of single-phase flow. It is shown that the uneven distributions result in a significant deterioration of the heat transfer performance. The relationship between the flow maldistribution characteristics and the resulting loss in heat exchanger effectiveness has been studied in this work. Certain improved header configurations with perforated plates were proposed in order to solve the maldistribution problem. It was found that the new header configurations could effectively improve the thermal performance of plate-fin heat exchangers. By changing the header configuration, the degree of flow and temperature nonuniformity in the plate-fin heat exchanger was reduced to 16.8% and 74.8%, respectively, under the main test condition.