This study investigated vortex-induced vibrations of marine risers in Ocean Thermal Energy Conversion systems. Flume experiments were conducted under two conditions: Condition 1 was with a fixed riser bottom, and Condition 2 was with a fixed bottom on a mooring platform. The cross-flow acceleration of the riser was measured at different current velocities, and corresponding vibration responses were analyzed. Numerical simulations based on the flume experiments were employed to validate the reliability of the simulation method. Results from the flume experiments revealed vortex-induced resonance in Condition 1 when the flow velocity approached the riser’s natural frequency. In Condition 2, similar vibration responses were observed, with maximum acceleration occurring during flow velocity-induced vortex-induced vibrations. However, at higher flow velocities, the acceleration response showed a decrease followed by an increase, indicating the excitation of higher-order modes. The numerical simulations matched the flume experiments in Condition 1. In Condition 2, while the acceleration response and frequency agreed during vortex-induced resonance, discrepancies arose in the flow velocity that caused vortex-induced vibrations compared to the flume experiments. This study demonstrated the accuracy of numerical simulations in reflecting vortex-induced vibrations of risers, providing a foundation for further research on complex riser systems.