Improving work zone road safety is an issue of great interest due to the high number of crashes observed in work zones. Departments of Transportation (DOTs) use a variety of methods to inform drivers of upcoming work zones. One method used by DOTs is work zone signage configuration. It is necessary to evaluate the efficiency of different configurations, by law, before implementation of new signage designs that deviate from national standards. This research presents a driving simulator based study, funded by the Missouri Department of Transportation (MoDOT) that evaluates a driver’s response to work zone sign configurations. This study has compared the Conventional Lane Merge (CLM) configurations against MoDOT’s alternate configurations. Study participants within target populations, chosen to represent a range of Missouri drivers, have attempted four work zone configurations, as part of a driving simulator experience. The test scenarios simulated both right and left work zone lane closures for both the CLM and MoDOT alternatives. Travel time was measured against demographic characteristics of test driver populations. Statistical data analysis was used to investigate the effectiveness of different configurations employed in the study. The results of this study were compared to results from a previous MoDOT to compare result of field and simulation study about MoDOT’s alternate configurations.