It has been suggested that some patients with cirrhosis are unfit to operate a motor vehicle. However, performance while driving a motor vehicle has not been evaluated in such patients. In this pilot study, we assessed the fitness to drive of stable individuals with cirrhosis and clinical evidence of portal hypertension, portal-systemic shunting and no prior history of hepatic encephalopathy. We examined 15 ambulatory patients with cirrhosis together with 15 age-, educational level- and driving experience-matched healthy controls. Neuropsychological testing was performed with the Reitan trail test, block design and digit symbol tests as well as visual reaction time. A driving test in the laboratory used a film to measure complex visual reaction time (reaction to road symbols) and threat recognition (accident avoidance). Driving on the road was assessed by a licensed Illinois state driving evaluator. Penalty points were given according to 11 standardized driving categories. As a group, patients with cirrhosis had no significant differences in their performance on a simulator or during actual driving conditions when compared to matched controls. Sixty-six percent of the subjects with cirrhosis had two or more abnormal neuropsychological tests, a criterion used to define the presence of subclinical encephalopathy. No deficiencies in simulated or real driving performance was seen when compared to patients with cirrhosis with normal neuropsychological tests. In this study, stable subjects with cirrhosis and evidence of portal hypertension, portal-systemic shunting, abnormal neuropsychological tests and no prior history of overt encephalopathy did not exhibit a major impairment in their fitness to drive.