Crashes with large animals pose demands on vehicle design beyond standardised crash test methods. In some parts of the world, crashes with large animals are frequent and involve a relatively high risk of injury. The objective of this study is to identify the significance of the occurrence and the challenges of crashes with large animals, including evaluations using a crash test method simulating a vehicle‐to‐large animal crash. Statistics identify several important factors, such as impact speed, impact configuration, environmental factors and driver awareness. Occupant injuries of special focus are injuries to head, neck and upper extremities both by penetrating roof structure parts and by interaction with the large animal body, and cuts and scrapes by splintering glass or sharp edges. Tests using a large animal dummy illustrate the importance of structural integrity of the header and A‐pillar area, as well as vehicle speed at impact. An increased impact speed not only drives the structural intrusion depth but also influences the timing of head impact towards the deformed area. As a complement to structural and restraint designs, future safety development challenges also include aspects of detecting and sensing large animals addressing occupant protection by mitigating and potentially avoiding the crash.