Air exchange in pressurized water pipelines is an essential but complex aspect of pipeline modeling and operation. Implementing effective air management strategies can yield numerous benefits, enhancing the system’s energy efficiency, reliability, and safety. This paper comprehensively evaluates an irregular profile pipeline filling procedure involving air-release through an air valve. The analysis includes real-time data tests and numerical simulations using Computational Fluid Dynamics (CFD). A Digital Twin model was proposed and applied to filling maneuvers in water installations. In particular, this research considers an often-overlooked aspect, such as filling a pipe with an irregular profile rather than a simple straight pipe. CFD simulations have proven to capture the main features of the transient event, which are suitable for tracking the air-water interface, the unsteady water flow, and the evolution of the trapped air pocket. Thus, they provide thorough and reliable information for real-time operational processes in the industry, focusing on the filling pressure and geometry of the air-valve hydraulic system. Additionally, this study provides details regarding the application of an efficient Digital Twin CFD approach, demonstrating its feasibility in optimizing the filling procedure in pipes with irregular profiles.