Objectives Cable median barriers (CMBs) are installed on freeway medians to prevent cross-median crashes and reduce the severity of median-related crashes. Though CMBs are effective in preventing cross-median crashes, they are also known to increase the number of property damage–only (PDO) crashes. The higher frequency of PDO crashes could result in increased CMB maintenance and repair expenses. The aim of this study is to evaluate the safety impact and economic justification of CMBs in Louisiana. Methods Initially, a flowchart was developed using Louisiana crash data to identify targeted crashes, such as median-related and cross-median crashes. This was followed by a 3-year observational before-and-after crash analysis with an emphasis on head-on collisions and crashes involving large trucks. Using a 4-step improved prediction method, crash modification factors were then developed to quantitatively assess the impact of CMBs on crash outcomes, accounting for and adjusting to changes in the annual average daily traffic (AADT) and relevant crash frequencies before and after CMB implementation. Finally, an exhaustive benefit–cost analysis was conducted to determine the cost-effectiveness of CMBs. Results The results revealed that CMBs significantly reduced cross-median crashes of all severities. However, an increase in PDO crashes was observed in both total and median-related crashes. Large truck cross-median crashes and head-on collisions also decreased significantly after CMB implementation. Testing Level 4 (TL-4) CMBs were found to be more effective in preventing vehicles from crossing the median and in reducing crashes of higher severity levels. The benefit–cost ratios, calculated using economic crash unit costs for both total and targeted crashes, were greater than 1. Notably, the estimated benefit–cost ratios were considerably higher, demonstrating that CMBs are cost-effective countermeasures for enhancing traffic safety. Conclusion This study contributes to the understanding of CMB performance from both traffic safety and economic perspectives. The findings may assist transportation agencies in making decisions regarding the management of CMB systems. Based on the comprehensive analysis of CMBs on Louisiana freeways, this project has revealed that CMBs are an effective and economically justified crash countermeasure. Thus, further implementation of CMBs is recommended until better alternatives are available.