Objective: Accounting for one fifth of all crashes and one sixth of all fatal crashes in the United States, intersection crashes are among the most frequent and fatal crash modes. Intersection advanced driver assistance systems (I-ADAS) are emerging vehicle-based active safety systems that aim to help drivers safely navigate intersections. The objective of this study was to estimate the number of crashes and number of vehicles with a seriously injured driver (Maximum Abbreviated Injury Scale [MAIS] 3+) that could be prevented or reduced if, for every straight crossing path (SCP) intersection crash, one of the vehicles had been equipped with an I-ADAS. Methods: This study retrospectively simulated 448 U.S. SCP crashes as if one of the vehicles had been equipped with I-ADAS. Crashes were reconstructed to determine the path and speeds traveled by the vehicles. Cases were then simulated with I-ADAS. A total of 30 variations of I-ADAS were considered in this study. These variations consisted of 5 separate activation timing thresholds, 3 separate computational latency times, and 2 different I-ADAS response modalities (i.e., a warning or autonomous braking). The likelihood of a serious driver injury was computed for every vehicle in every crash using impact delta-V. The results were then compiled across all crashes in order to estimate system effectiveness. Results: The model predicted that an I-ADAS that delivers an alert to the driver has the potential to prevent 0-23% of SCP crashes and 0-25% of vehicles with a seriously injured driver. Conversely, an I-ADAS that autonomously brakes was found to have the potential to prevent 25-59% of crashes and 38-79% of vehicles with a seriously injured driver. I-ADAS effectiveness is a strong function of design. Increasing computational latency time from 0 to 0.5 s was found to reduce crash and injury prevention estimates by approximately one third. For an I-ADAS that delivers an alert, crash/injury prevention effectiveness was found to be very sensitive to changes in activation timing (warning delivered 1.0 to 3.0 s prior to impact). If autonomous braking was used, system effectiveness was found to largely plateau for activation timings greater than 1.5 s prior to impact. In general, the results of this study suggest that I-ADAS will be 2-3 times more effective if an autonomous braking system is utilized over a warning-based system. Conclusions: This study highlights the potential effectiveness of I-ADAS in the U.S. vehicle fleet, while also indicating the sensitivity of system effectiveness to design specifications. The results of this study should be considered by designers of I-ADAS and evaluators of this technology considering a future I-ADAS safety test.