Objective. To systematically review the effect of Acetyl-L-Carnitine in patients with hepatic encephalopathy. Material and methods. Design: systematic review and meta-analysis. Data sources: The Cochrane Library, MEDLINE, EMBASE.com, Science Citation Index, Google search and the China Biological Medicine Database to June 2012. Review methods: randomized placebo controlled trials of Acetyl-L-Carnitine in patients with hepatic encephalopathy assessing whether Acetyl-L-Carnitine an effective therapy or not. No language restrictions were applied. Two reviewers independently extracted data and assessed quality. Results. 7 methodologically sound randomized controlled trials were identified involving 660 participants with hepatic encephalopathy, totaling 249 with subclinical hepatic encephalopathy, 189 with West Haven grade 1, 162 with West Haven grade 2 and 60 with West Haven grade 3. Acetyl-L-Carnitine was effective to improve serum ammonia level (weighted mean difference 25.90, 95% confidence intervals 20.89 to 30.91, P < 0.05) and the number connection test completion time (weighted mean difference 16.62, 95% confidence intervals 9.88 to 23.36, P < 0.05). The outcome was consistent in subgroup analyses. No publication bias was detected. Adverse events were reported infrequently and were minor. Conclusions. Acetyl-L-Carnitine is promising as an effective and tolerable treatment for hepatic encephalopathy that associated with improved serum ammonia levels and the number connection test.