Work zone Intrusion Alert Systems (WZIAS) are alert mechanisms that detect and alert workers of vehicles intruding into a work zone. These systems pre-dominantly employ two components-sensors placed near the work zone perimeter that detect intrusions, and alarms placed closed to or carried by the workers that alerts them. This study investigates the association between layout of these components for three WZIAS on work zone crashes based on worker reaction. Also, the key determinants of work zone crashes in presence of the WZIAS is identified using survival analysis. The ideal deployment strategy and use case scenarios for the three WZIAS is presented based on the findings of the study. The systems were subjected to rigorous testing that emulated intrusions to record worker reaction and determine occurrence of crashes. Analysis of results indicate that the key determinants of work zone crashes are speed of the intruding vehicle, distance between the sensor and worker, and accuracy of a system in detecting intrusions and alerting workers. Results from field experiments suggest that identification of appropriate use cases for WZIAS is necessary to ensure they work effectively. Based on the findings from this study it is suggested that current guidelines on work zones be modified to standardize WZIAS setup.