Many work zones require lane closures, and road users need to be notified of these closures through appropriate upstream signage. A literature review prepared for this study found several previous investigations indicating insufficient comprehension of the U.S. standard lane closure sign (designated in the Manual on Uniform Traffic Control Devices for Streets and Highways [MUTCD] as W4-2) and similar signs used internationally. The W4-2 sign is also unsuitable for signing interior lane closures on roadways with three or more lanes. Driver comprehension of several alternative sign faces was tested through a survey using the ANSI Z535.3 process and was followed by a driving simulator study. The driver comprehension survey suggests that an Upward Drop Arrow design is a promising alternative to the existing W4-2 sign for sites where two upstream lanes are reduced to one lane in the work zone. In addition, one-arrow-per-lane signs developed as Americanized versions of the Vienna Convention G12a sign template are a promising option for interior lane closures on multi-lane roadway segments. A driving simulator study compared the W4-2, a MERGE text sign with a horizontal arrow, and an Americanized version of the Vienna Convention G12a sign. In terms of sign comprehension, the W4-2 was the least understood of the three signs. The W4-2 resulted in more late merge maneuvers than the other two signs. Field evaluation of the Upward Drop Arrow and Americanized G12a signs is recommended as a follow-up to this study.