Three dimensional responses of riser subjected to Vortex Induced Vibration (VIV) are investigated. Proportionality relations of stress and fatigue damage are mentioned. A computer code has been developed for time domain modeling of VIV of riser accounting for both Cross-Flow (CF) and In-Line (IL) vibration. The wake oscillator model is used to calculate the VIV of each strip. The wake oscillators are coupled to the dynamics of the long riser, while the Newmark-beta method is used for evaluating the structural dynamics of riser. The wake dynamics, including IL and CF vibrations, is represented using a pair of non-linear Van der Pol equations that solved using modified Euler method. The existing experimental and numerical results for stepped and sheared current are used to validate the proposed model and the results show reasonable agreement. The proposed model was implemented on Amir-Kabir semi-submersible riser deployed at the water depth of 713 meters of Caspian Sea. CF/IL VIV of this riser is simulated for various current velocities. The results show that although displacement amplitude of IL direction is lower than CF direction but because of higher curvature, stress values of IL direction for some cases can be higher than CF direction. Also because of higher frequency of IL direction, fatigue damage of this direction can be higher than CF one in some cases. It is shown that with increasing of current velocity; however, variation of displacement amplitude of two directions is low but stress increased and fatigue damage also increased with higher rate. For lower velocities which the modes are controlled with tension, stress and fatigue damage of IL direction is higher than CF direction. © JVE INTERNATIONAL LTD.