The Rural Intersection Active Warning System (RIAWS) is an innovative road safety treatment designed to slow traffic on major approaches to a high-risk rural intersection when vehicles are turning or crossing into or out of the side roads, thus reducing fatal and serious casualties. A 2 × 2 experimental driving simulation study was undertaken which aimed to determine the impact of signage (RIAWS versus traditional painted) and sign content (80 km/h versus slow down) on drivers’ instantaneous speed at rural intersections. The driving simulator assessment was completed by 96 drivers aged between 18 and 80 years with a current WA C class licence (passenger vehicle). This provided a total of 384 observations. The results of a two-way ANOVA found a significant interaction effect between speed signage and sign content (F(1,3) = 11.78, p < 0.001). The RIAWS “80 km/h” sign resulted in significantly lower instantaneous speeds than all other types of signs including RIAWS “slow down signs (p < 0.001), traditional painted “80 km/h” signs (p = 0.023) and traditional painted “slow down” signs (p = 0.001). Overall, the study found that RIAWS “80 km/h” sign and not the RIAWS “slow down” sign provided the most effective option for reducing driver speeds on approach to rural intersections. Further research is needed to determine the most effective placement of the RIAWS “80 km/h” signs and how they perform on curved roads.