Background: Ankle sprain lesions are the most common ligament lesions in humans. One particularly dangerous consequence of this pathology is an inability to quickly and sufficiently depress the brake pedal when driving a car. The high incidence of the lesion, in the context of a society that is highly automobile-dependent, makes the question "When can a patient safely drive a car again?" of particular socioeconomic importance. Hypothesis/Purpose: Though orthopaedic physicians are often confronted with this question, finding an answer in the sparse literature on the topic proves difficult. This study aims to provide a definitive answer to this question. Study Design: Prospective Case Control Study. Methods: 30 patients with grad II and III ligament injuries of the right ankle (18 women, 12 men) and 30 healthy volunteers (19 women, 11 men) participated in this study. Brake reaction time (BRT) was assessed using a previously reported custom-made driving simulator. BRT was assessed two, four and six weeks after injury. Simultaneously the American Orthopedic Foot and Ankle Society Ankle Hindfoot Score (AOFAS-AHS) was assessed. Results: Two weeks after the incident, the patients' BRT measured 690.6 ±186.2ms. Four weeks after the incident, the BRT improved to 551.8 ±137.3ms (p < 0.001). Compared to the healthy controls' BRT (553.6 ±118.6ms), there were no significant differences 4 weeks after the injury (p = 0.473). At this time, the BRT of both groups was also well below (i.e. faster) than the recommendations of road authorities (70 0-150 0ms). An AOFAS-AHS score of more than 80 points correlated with a sufficient BRT. Conclusions: Four weeks post injury, patients generally had a sufficient BRT to drive in traffic safely. Some patients could achieve sufficient BRTs at an earlier stage. All patients with sufficient BRTs had an AOFAS-AHS score of ≥81 points. The AOFAS-AHS score can therefore be regarded as an adequate screening tool to evaluate which patients are ready to safely operate motor vehicles earlier.