Current requirements for rear underride guards on large trucks are set by the National Highway Traffic Safety Administration in Federal Motor Vehicle Safety Standards (FMVSS) 223 and 224. The standards have been in place since 1998, but their adequacy has not been evaluated apart from two series of controlled crash tests. The current study used detailed reviews of real-world crashes from the Large Truck Crash Causation Study to assess the ability of guards that comply with certain aspects of the regulation to mitigate passenger vehicle underride. It also evaluated the dangers posed by underride of large trucks that are exempt from guard requirements. For the 115 cases meeting the inclusion criteria, coded data, case narratives, photographs, and measurements were used to examine the interaction between study vehicles. The presence and type of underride guard was determined, and its performance in mitigating underride was categorized. Overall, almost one-half of the passenger vehicles had underride damage classified as severe or catastrophic. These vehicles accounted for 23 of the 28 in which occupants were killed. For the cases involving trailers with underride guards compliant with one or both FMVSS, guard deformation or complete failure was frequent and most commonly due to weak attachments, buckling of the trailer chassis, or bending of the lateral end of the guard under narrow overlap loading. Most of the truck units studied qualified for at least one of the FMVSS exemptions. The two largest groups were trailers with small wheel setbacks and single-unit straight trucks. Dump trucks represented a particularly hazardous category of straight truck. The current study suggests several weaknesses in the rear underride guard regulation. The standard allows too much ground clearance, the quasi-static test conditions allow guard designs that fail in narrow overlap crashes, and certifying guards independent of trailers leads to systems with inadequate attachment and chassis strength. Additionally, the regulation should be expanded to cover a higher percentage of the large truck fleet.