Vortex-induced Vibrations (VIV) on long-span suspension bridges have become increasingly prevalent in recent years. The specific mechanisms of VIV on box girder bridges and efficient counter-measures for the VIV that are practical for bridge engineering applications have yet to be proposed. This research focuses on exploring the initiation mechanisms of the VIV on long-span box girder suspension bridges, determining how the VIV affects the comfort level for drivers and passengers in vehicles traveling on bridges with VIV, and proposing measures that can effectively detect and mitigate the VIV on long-span box girder suspension bridges. The overarching goal is to amplify the mechanistic understanding of VIV on long-span suspension bridges and inform the optimization of structural design to advance driving safety and passenger comfort subjected to VIV. A prototypical box girder suspension bridge with a main span of 1760 m is used as the engineering background for this research, and the dynamic characteristics of the bridge are analyzed with the Finite Element Method (FEM) and wind tunnel experiments to set as the foundation for the rest of the research. Three topics are investigated:1) To elucidate the VIV initiation mechanism for long-span suspension bridges, several box girder sections, including the rectangular girder sections, the rectangular girder sections with wind noses, and the streamlined box girder section of the prototypical bridge are tested in wind tunnel laboratories to observe their respective VIV performances and the effectiveness of various aerodynamic VIV mitigation measures. VIV initiation mechanisms of the box girder sections are explored in CFD analysis by recognizing vortexes and tracking their paths around the girder sections using two different methods. The influence of the Reynolds number effect is discussed with experimental results from wind tunnel experiments of girder sections with different scaling factors. 2) To characterize the driving and riding comfort level on bridge with VIV, a wind-traffic-vehicle coupled vibration model is established to determine the accelerations experienced by drivers and passengers in moving vehicles traveling on bridges with VIV, the comfort level is evaluated using two indices, including the Overall Vibration Total Value (OVTV) and the Motion Sickness Index (MSI). 3) Several mechanical VIV mitigation measures are proposed and tested on girder section models in the FEM model of the prototypical bridge. An effective mitigation measure consisting of a V-shaped damping cable connecting the main cables on the main span and side span with a rotational damping device at the tower-girder intersection is tested and validated. The equivalent damping capability of girder-end bearing support friction force is analyzed and its potential in mitigating VIV is discussed. A VIV dynamic characteristics detection method based on machine learning and visual recognition is developed, and the functionalities are tested with a video of a bridge vibrating under the influence of VIV as well as a simulation animation of bridge with VIV.