Background: Subclinical Hepatic Encephalopathy (SHE) is a subclinical syndrome of neuropsychological and neurophysiological deficit in patients with liver disease that cannot be detected by routine clinical testing.Objective: To study the efficacy of lactulose for the treatment of cirrhotic patients with SHE.Patients and Methods: A total of 91 cirrhotic patients, 50 males and 41 females were included in this study.  The majority 92.3% were CTP class A and 7.69% class B; age 32-82 years old.  The diagnosis of SHE was made by electroencephalogram (EEG) and quantitative psychometric test [Number Connection Test (NCT), Digit Symbol Test (DST) and Block Design Test (BDT)].  Abnormalities at least 2/3 of psychometric tests or abnormal EEG findings were the criteria used for diagnosis of SHE.Results: Thirty (27.3%) patients were diagnosed as SHE; 10 patients were excluded from the study because five were not cooperative, four deteriorated from HE, and one died from severe cellulitis with septic shock. Out of 30 patients with SHE, only 20 were recruited in the study.  Double-blind randomized study on the efficacy of lactulose vs placebo in 20 SHE patients was conducted; 11 were randomized to treatment group (lactulose 30-45 ml/day for 2 months) and 9 to placebo group (placebo 30-45 ml/day for 2 months).  Psychometric tests and EEG were performed in all patients in both groups after two months.  Improvement of psychometric test, BDT, was 4 (36.3%) in the treatment group and 4 patients in the placebo group (44.4%) (p = 0.192).  Improvement of DST was 4 (36.3%) in the treatment group and 3 patients in the placebo group (33.3%), (p = 1.000). Mean NCT time pre and post treatment in the treatment group and placebo were 145.9 ± 79.5 : 167 ± 164.8 sec and 115.7 ± 71.8 : 102.4 ± 65.5 sec (p = 0.302), respectively.  EEG improvement in the treatment group was 2 (18.1%) compared to none in the placebo group, (p = 0.479).Conclusions: For cirrhotic patients with SHE, lactulose was not able to improve psychometric tests and EEG.