To explore the influence of the isolation ball in a crude oil pipeline running over complex terrain, a “U” undulating crude oil pipeline with a large drop was taken as a practical case (the maximum elevation difference was 1490 m). Based on the OLGA multiphase flow transient simulation method, this paper conducts a simulation study on the process of pushing water in a large drop crude oil pipe section. The effect of oil–water interface pig (isolation ball) in the process of pushing water from crude oil and the influence of key parameters such as isolation ball diameter were analyzed. the movement characteristics of the pig in the large-drop sections under the conditions of various throughputs and fluid volumes were studied and determined the maximum velocity, pressure, fluid-holding rate, travel distance, and slug behavior of the pig at various low points. The results show that in the selected pipe section, when the throughput was 900 m3/h to 2500 m3/h, the presence of the isolation ball reduced the mixture of oil and water by 84.2% to 93.7%, reduced the volume of gas generated by the vaporization of the light oil components during transport, and reduced the slug flow in the pipe, providing an effective basis for designing optimal conditions for crude oil pipeline transport.