The Ripuluo crude oil pipeline has a total length of 798 km, with a maximum elevation difference of 132 m within a 6 km section along the line. It is commissioned by introducing oil after creating an isolated water section. During the commissioning process, issues such as gas accumulation at pipeline high-point and water accumulation at pipeline low-point are likely to occur in the pipe section with large elevation drop, which poses a threat to safe pipeline production. In this paper, the Ripuluo crude oil pipeline commissioning model is set up using OLGA software to analyze the pressure changes of the pumping stations during the pipeline commissioning process of water-replacing-gas and oil-replacing-water, the influence of different pipeline flow-rate and water-filled length on the pressure at the turning point, the liquid holdup and the low point water holdup. The results show that when the pipeline flow-rate is 1 440 m3/h and the minimum water-filled length reaches 70 km; the changes in the pressure at the pipeline turning point, and the liquid and water holdup at the low point can meet the safety requirements. It is recommended that if conditions permit, the water-filled length should be extended to the distance between the stations or the full pipeline length, which can further enhance the safety in commissioning process and trial operation. The research results can effectively guide the formulation of other pipeline commissioning plan and ensure the safety of pipeline’s commissioning.