Objectives Many studies have demonstrated that patients with Obstructive Sleep Apnea Syndrome (OSAS), a very common sleep-related breathing disorder, are usually impaired in their driving ability because of decreased sleep quality. However, most of the simulation procedures in laboratories are designed to create monotonic conditions with low traffic density, if any, thereby leading to a dramatic decrease in performance in OSAS patients because of the lack of stimulation. The aim of this study was therefore to evaluate driving abilities in OSAS patients involved in a driving simulation task with medium traffic density, in order to replicate as far as possible real world conditions. The behavioral and physiological attributes likely to predict driving performance in these patients were also investigated. Methods After a normal night of sleep, 12 OSAS patients and 8 healthy controls performed 6 driving sessions during a 24-h period of sustained wakefulness. Driving performances (speed, lateral position, distances…) were measured and correlated to sleep parameters and to a waking EEG recorded during the task. Results Compared to controls, patients showed difficulties in speed adjustment. However, they maintained longer inter-vehicle distances, including during overtaking. Their waking EEG, while driving, showed increased spectral power in theta (3.9–7.8Hz) but also in beta (12.7–29.2Hz) activity, alpha power (7.9–12.6Hz) being increased in both groups due to sustained wakefulness. Poor sleep indices were correlated to increased theta and beta activities, as well as to more cautious behavior. Discussion In medium traffic density conditions, driving performance in OSAS patients remained at near normal levels, but with more cautious behavior than controls. This could be the result of a bigger effort to stay awake, as suggested by an increased beta activity in these patients.