Previous research has shown that traveling in a work zone involves a higher risk of crashing compared to normal (non-work zone) driving conditions. Research further suggests that the severity of work zone crashes is greater on average than non-work zone crashes. The period of time in which the traffic control is being set up, removed, or modified for a work zone is also considered a critical situation where workers and motorists are exposed to risks, especially during the transition period. This study aimed to examine the safety hazards and risks associated with traffic control operations during the set-up, modification, and removal of temporary traffic control, and to develop guidance for enhancing safety as the temporary traffic control placement and removal takes place. To fulfill the research goal, the researchers established a research protocol involving four research methods: a comprehensive literature review on the study topics, a survey of state department of transportation (DOT) and highway construction and contractor personnel, focus group interviews of contractors and DOT personnel, and on-site observations of traffic control placement and removal operations. The results from the literature review expose limited guidance and standard procedures for setting up and removing traffic control available to state DOTs and contractors. In addition, the survey results reveal hazardous steps in the traffic control operation that create life-threatening hazards to workers and motorists, such as in a situation where a traffic control device is being initially placed to form a lane closure. Results from both focus group interviews conducted revealed interesting findings that nighttime work zone traffic control operation is perceived to be more dangerous than daytime traffic control operation. Furthermore, the site observation results show other work elements associated with the traffic control process that were identified to be risky for workers and motorists during the traffic control operation. An example of those identified elements included: misleading arrow sign indication mounted on truck, wrong sequence order of sign installation, reading traffic control plan while driving to work zone, among others. To mitigate the risks identified in the operation, the researchers proposed several potential treatments, including placing a radar speed board with a portable changeable message sign (PCMS) in advance of the “Road work Ahead” signs, placing blue lights on cone devices, and implementing a rolling slowdown for initial sign set-up operation in a work zone, along with the given treatment analyses table for addressing high risk and moderate risk conditions to enhance safety during the traffic control operation in work zones. Further recommendations on best practices for state departments of transportation and roadway contractors are provided.