U-bends are frequently employed in industries to change the direction of fluid flow. Flow Induced Vibrations (FIV) are very prominent due to internal two-phase flow and vary with U-bend orientation. Potential possibilities of spatial orientations of a U-bend make it impractical to predict these vibrations using an experimental approach. This study investigates the two-phase flow-induced vibrations for 0°, 30°, 60° and 90° upward flow in a U-bend using CFD. In-plane and out-of-plane directional vibrational data was gathered for these four orientations of U-bend. For constant superficial velocities with void fraction of 0.5, impact of orientation on slug frequencies was observed with Fast Fourier Transformation. In-plane (x-axis) forces applied at the outlet bend significantly increase 39 compared to the corresponding forces at the inlet bend. Forces at the outlet bend along the y-axis (out-of-plane) were reduced by 26, but the forces along the z-axis show a more moderate decrease of 7. This study provides significant data essential to forming a correlation of two-phase flow-induced vibrations with multiple upward flow U-bend orientations. © 2024, Semarak Ilmu Publishing. All rights reserved.