Background & Aims: Cirrhotic patients with minimal hepatic encephalopathy (MHE) show impaired driving ability and increased vehicle accidents. The neurological deficits contributing to impair driving and the underlying mechanisms are poorly understood. Early detection of driving impairment would help to reduce traffic accidents in MHE patients. It would be therefore useful to have psychometric or biochemical parameters reflecting driving impairment. The aims of this work were as follows: (i) to shed light on the neurological deficits contributing to impair driving; (ii) to assess whether some psychometric test or biochemical parameter is a good indicator of driving impairment. Methods: We assessed in 22 controls, 36 cirrhotic patients without and 15 with MHE, driving performance using a driving simulator (SIMUVEG) and Driver Test. MHE was diagnosed using the psychometric hepatic encephalopathy score (PHES). Psychometric tests assessing different neurological functions (mental processing speed, attention, visuo-spatial and bimanual coordination) were performed. Blood ammonia and parameters related with nitric oxidecGMP metabolism, IL-6, IL-18 and 3-nitrotyrosine were measured. Results: Patients with MHE showed impaired driving ability correlating with MHE grade, with impaired vehicle lateral control in spite of reduced driving speed. Patients with MHE show psychomotor slowing, longer reaction times, impaired bimanual and visuo-spatial coordination and concentrated attention and slowed speed of anticipation and increased blood ammonia, cGMP, IL-6, IL-18 and 3-nitrotyrosine. Conclusions: Impaired mental processing speed, attention and alterations in visuo-spatial and motor coordination seem main contributors to impaired driving ability in patients with MHE. Increased serum 3-nitrotyrosine is associated with impaired driving ability.