This paper presents an engineering investigation on the impact of well trajectory on production performance of ESP-lifted shale wells. A representative set of field data was selected as the input data to model the shale well with an ESP installed. Based on these data, a comprehensive analysis of production performance from ESP-lifted shale wells was performed. These wells had the same or similar reservoir characteristics, but different well trajectories including relatively smooth and highly sinuous toe-up and toe-down well trajectories. A transient dynamic multiphase simulator was used to perform the engineering investigation by integrating ESP performance and wellbore models over the life of a shale well, evolving from initial steady natural flow production to late-life unsteady and slugging flow production. From the analysis, the well trajectory does not impact the well production performance of an ESP-lifted well. The slugging flow results in a dramatic gas volume fraction changing from 0 to up to 100% at the pump intake. The study combines multiphase transient modeling (for the specific well trajectory) with reservoir modeling and historic production data. The analysis includes models of the well behavior and instabilities that allow operators to evaluate the application of ESP systems considering well trajectory and optimize timing for installation and withdrawal.