The effect of partial sleep deprivation (PSD) on driving abilities, as measured with a driving simulator, and the value of slow-release caffeine as a countermeasure to the expected performance decrements, were studied. Twelve subjects, between 20 and 25 years of age, underwent four experimental conditions, 4.5 or 7.5 h time in bed (TIB) with 300 mg slow-release caffeine or placebo, according to a Latin square design. Driving performance was measured twice by a 45-min driving task on a simulator. Subjective sleepiness/alertness and mood were assessed four times, by means of the Stanford Sleepiness Scale (SSS) and Profile of Mood States (POMS). After 4.5 h as compared with 7.5 h TIB lane drifting and speed deviation were higher, but only the effect on the first variable reached significance. In the placebo condition at 13.00 h, accident liability increased after PSD. Subjective sleepiness was higher in the 4.5 h TIB group. Caffeine intake gave rise to a decrease in lane drifting and after PSD it led to a smaller speed deviation and accident liability. The findings suggest that a lack of sleep can lead to a significant driving performance impairment, with drivers having problems to maintain an appropriate road position and a posted speed and more drivers getting involved in an accident. Secondly, the results indicate that caffeine – more specifically slow-release caffeine – can serve as a valuable countermeasure to these performance decrements, in the absence of any important side-effects, especially when its application is of an acute nature and when there is no opportunity to take a nap.