Patients with chronic obstructive pulmonary disease (COPD) present with impairments of their cognitive performance. It is still unknown whether cognitive deficits influence driving abilities in patients with COPD. The present study investigates driving performance in patients with COPD and healthy controls. Driving simulation was performed in 17 patients with COPD and 10 healthy controls. Patients with COPD demonstrated significantly worse results in terms of accident frequency in the simulated driving situation. No correlations existed between the severity of disease, assessed from the polysomnographical findings (e.g., lung function, blood gas analysis, sleep disturbance, nocturnal ventilation, and oxygen saturation), and driving performance. We conclude that impairments of driving performance in patients with COPD cannot be predicted on the basis of the severity of the disease. The impairment of driving performance in the simulated driving situation in COPD patients may have crucial consequences for driving licensing in these patients.