OBJECTIVE Minimal hepatic encephalopathy (MHE) is common in patients with extrahepatic portal vein obstruction (EHPVO). There is no study on the treatment of MHE using lactulose in patients with EHPVO. METHODS Consecutive EHPVO patients were assessed by psychometric (number connection test (NCT-A and B), digit symbol test (DST), serial dot test (SDT), line tracing test (LTT)), and critical flicker frequency (CFF) at inclusion. Patients diagnosed as MHE were treated with lactulose and psychometric tests, CFF, and were reassessed after 3 months. RESULTS Of the 70 patients screened, the prevalence of abnormal psychometric test was as follows: NCT-A (41%), NCT-B (53%), DST (38%), SDT (40%), and LTT (44%). Thirty patients (43%) had two or more than two abnormal (>2 SD) psychometry tests. Lactulose improved MHE in 16/30 (53%) of patients after 3 months of treatment. Arterial ammonia decreased after lactulose treatment compared to baseline (83.7±19.1 vs. 65.1±19.3 μmol/l, P=0.001). A total of 9 (75%) of 12 patients with large spontaneous shunt and 7 (39%) of 18 patients without spontaneous shunt improved with lactulose (P=0.07). CFF in patients with MHE (n=30) was significantly lower than those without MHE (n=40) (38.1±2.4 vs. 41.5±3.1 Hz, P=0.01). CFF was less than 38 Hz in 21 (70%) of 30 patients before treatment and in 10 (33%) patients after lactulose therapy in MHE patients. All patients could tolerate lactulose without any significant side effects. Four patients (13%) developed transient diarrhea in whom dose needed reduction, 3 (10%) did not like its taste but have continued, and 2 (6%) developed abdominal bloating sensation. CONCLUSIONS Lactulose is effective in the treatment of MHE in patients with EHPVO.