The Highway Safety Manual (HSM) is the compilation of national safety research that provides quantitative methods for analyzing highway safety. The HSM presents crash modification functions related to freeway work zone characteristics such as work zone duration and length. These crash modification functions were based on freeway work zones with high traffic volumes in California. When the HSM-referenced model was calibrated for Missouri, the value was 3.78, which is not ideal since it is significantly larger than 1. Therefore, new models were developed in this study using Missouri data to capture geographical, driver behavior, and other factors in the Midwest. Also, new models for expressway and rural two-lane work zones that barely were studied in the literature were developed. A large sample of 20,837 freeway, 8,993 expressway, and 64,476 rural two-lane work zones in Missouri was analyzed to derive 15 work zone crash prediction models. The most appropriate samples of 1,546 freeway, 1,189 expressway, and 6,095 rural two-lane work zones longer than 0.1 mile and with a duration of greater than 10 days were used to make eight, four, and three models, respectively. A challenging question for practitioners is always how to use crash prediction models to make the best estimation of work zone crash count. To solve this problem, a user-friendly software tool was developed in a spreadsheet format to predict work zone crashes based on work zone characteristics. This software selects the best model, estimates the work zone crashes by severity, and converts them to monetary values using standard crash estimates. This study also included a survey of departments of transportation (DOTs), Federal Highway Administration (FHWA) representatives, and contractors to assess the current state of the practice regarding work zone safety. The survey results indicate that many agencies look at work zone safety informally using engineering judgment. Respondents indicated that they would like a tool that could help them to balance work zone safety across projects by looking at crashes and user costs.