Minimal hepatic encephalopathy (MHE) is characterized by disturbance of mental state and neuromuscular function. To assess the clinical efficacy of acetyl-L: -carnitine (ALC) in the treatment of MHE, we performed a randomized, double-blind, placebo-controlled study administering ALC in cirrhotic patients with this disease and evaluating their cognitive functions. One hundred and twenty-five cirrhotic patients, of whom 21 were infected by hepatitis B virus, 75 by hepatitis C virus and 29 with cryptogenic cirrhosis, were enrolled in our study. Patients were randomly divided into two groups, and using double-blind administration, group A was treated with ALC and group B with placebo for 90 days. The two groups were similar in demographic characteristics, aetiology of cirrhosis, duration and Child-Pugh grade. Minimal hepatic encephalopathy was diagnosed with the Trail Making Test (TMT), Symbol Digit Modalities Test (SDMT) and Auditory Verbal Learning Test (AVL) and cognitive function with the Mini Mental State Examination (MMSE). After 90 days in group A treated with ALC, we observed a significant decrease in prothrombin time (P < 0.001), bilirubin serum levels (P < 0.01), AST (P < 0.001), fasting NH(4) serum levels (P < 0.001), Trail Making Test-A (P < 0.001) and Trail Making Test-B (P < 0.001), and a significant increase in albumin serum levels (P < 0.005), MMSE test (P < 0.001), Symbol Digit Modalities Test (P < 0.001), BDT (P < 0.001), AVL long-term test (P < 0.001) and AVL total test (P < 0.001). No significant differences were observed in EEG in either group of patients treated with ALC or placebo. The benefits of ALC in comparison with placebo are demonstrated in greater reductions in serum ammonia levels, as well as in improvements of neuropsychological functioning.