The analysis of pressure changes in water and steam flow along the entire once-through steam boiler tube system was carried out. An efficient advanced method is developed and presented for the prediction of once-through boiler thermalhydraulics, which is based on the steam-water two-fluid model with mass, momentum and energy balance equations and mechanistic correlations for the steam-water interface transfer processes. The model is suitable for the fluid flow parameters prediction in the span from single and two-phase flow conditions under subcritical operating conditions to supercritical and near critical flow conditions. Conducted calculations provide detailed insight in the fluid pressure, velocity and temperature change in the boiler tube system. The numerical results are validated by comparison with data measured at the boiler tube system. The thermalhydraulic analysis shows that a significant increase in hydraulic resistance occurs in boiler evaporator tubes, while this increase in the steam superheater tubes is lower. The increase of hydraulic resistance in the evaporator tubes, both in the water heating zone and in the evaporation zone with the two phase mixture flow is due to the fouling deposited on the inner wall of tubes. The pressure drop in evaporating tubes almost doubles in comparison to the design values after the long operational period. The presented results are a support to boiler’s design, operational procedures and maintenance.