Police enforcement is sometimes used by U.S. transportation agencies for safety improvement in work zones. The important question that must be answered by those responsible for programming police enforcement in work zones is: where, when and how to enforce? This paper presents a research conducted by the Purdue Center for Road Safety (CRS) for the Indiana Department of Transportation (INDOT) aimed to develop a tool for selecting work zones, periods of enforcement, and enforcement strategies that maximize the safety benefit within the available budget. This research included modeling of the crash frequency in work zones to better understand work zone safety factors and evaluating several police enforcement strategies through a carefully designed police enforcement experiment in selected work zones. The study has confirmed several findings of the previous studies and it has provided new results such as finding that Variable Message Sign units are highly effective in reducing drivers’ speed inside work zones. The practical outcome of this effort described in this paper is the Work Zone Police Enforcement Programming Tool (PEPT) used by INDOT to program cost-effective police enforcement activities.