OBJECTIVES: Cirrhosis and its complications, such as hepatic encephalopathy (HE) are the sixth cause of general mortality in Mexico. The objective of this study is to evaluate a cost-effectiveness relationship of  medications used to treat hepatic encephalopathy from the perspective of the Mexican Institute of Social Security (IMSS). METHODS: Cost-effectiveness analysis of treatments used for acute hepatic encephalopathy, based in a decision tree model, and considering a temporal horizon of 14 days, from the perspective of public health institutions. Existing relevant therapeutic alternatives available at the IMSS are: lactulose, L-ornithine L-aspartate (LOLA), neomycin and rifaximin (the new alternative). Proposed effectiveness measure based on available published studies and based on evidence: Percentage of patients with improvement in signs and symptoms of hepatic encephalopathy. Only direct medical costs are considered for the analysis, obtained from unitary medical attention costs reported by IMSS. A univariated sensitivity analysis, using relevant variables (price and effectiveness) and discount's rates escenarios were performed. RESULTS: Treatment costs for each alternative (1 USD= 13.5 MXN $) totaled: lactulose US$3294, LOLA US$3297, neomycin US$3301 and rifaximin US $3312. In relation to effectiveness, the percentage of patients who presented improved signs and symptoms for each alternative is as follows: lactulose and LOLA 55%, neomycin 64% and rifixamin 90%. Cost effectiveness ratios are: lactulose US$5991, LOLA $5995, neomycin US$5157 and rifixamin US$3680. The incremental cost effectiveness analysis indicates that LOLA and neomycin are surpassed by lactulose and rifaximin, which are located on the efficiency line. Rifaximin can lessen hospital stays by at least one day and cut down at least one medical consultation. If these factors are taken into account for the sensitivity analysis, rifaximin takes the lead as dominating alternative. CONCLUSIONS: Rifaximin is a highly cost effective alternative for treating acute hepatic encephalopathy from an institutional perspective in Mexico