The slot width ratio of a twin-box girder plays an important role in the aerodynamic performance of the corresponding bridge. Therefore, it is necessary to investigate the VIV performance of a twin-box girder with various slot width ratios and evaluate the effectiveness of present VIV countermeasures considering the influence of different slot width ratio. Through a series of wind tunnel tests, the present study firstly investigated the VIV performance of a twin-box girder suspension bridge with six representative slot width ratios ranging from 0% to 100%. Then, four countermeasures, including increasing structural damping ratio, installing grid plates, wind barriers and guide vanes, were checked and comprehensively evaluated with the aim of identifying the most effective VIV control measure. The experimental results showed that the VIV performance of a twin-box girder with 0% slot width ratio (a single box girder) is superior to those with central slot. The maximum normalized heaving VIV amplitude occurs at the slot width ratio of 60% for the 1:60 geometrical scale model (around 0.093) and 80% for the 1:30 scale model (around 0.1), respectively. The significant difference of the torsional VIV responses between the two models with different geometrical scale is found at the slot width ratio of 20%. The comparison of VIV countermeasures for the 20% and 60% slot width ratios suggested that increasing damping ratio is helpful for reducing VIV responses, while installing guide vanes may have adverse effects. The application of grid plates and wind barriers can have positive effects in suppressing the heaving VIV responses, while the effectiveness of grid plates is more obvious with the decrease of grid porosity. Furthermore, the application of the grid plates with 0% grid porosity can perfectly enable the VIV performance of the twin-box girder bridge to meet the requirements of both Sperling indicator and Wind-resistance specification of China.