Autonomic neuropathy (AN) is common in patients with chronic liver disease. For hitherto unknown reasons, in longitudinal studies, the presence of AN has been found to be an independent predictor of mortality in patients with cirrhosis. We hypothesized that patients with AN are more likely to develop hepatic encephalopathy (HE) due to prologed intestinal transit time. In this study, we examined the incidence of new-onset HE in patients with and without AN. Seventy-two patients (Child A/B/C = 35/31/6) without evidence of HE at the time of autonomic function testing (AFT) were followed for 39.5 +/- 27.3 months. The end point of the study was the development of new onset HE. Patients were followed until death or liver transplantation. Of the 72 patients, 42 (58%) patients did not develop HE (group A) while 30 (42%) developed HE (group B) during the follow-up. Both groups had similar baseline demographics. AN was more common in group B (27/30; 90%) compared to group A (28/42; 67%) (P = 0.02). Kaplan-Meier analysis showed a trend toward a higher incidence of HE in patients with AN. Mortality was higher in group B (12/30; 40%) compared to group A (8/42; 19%) (P = 0.04). Patients with AN were more likely to develop new onset HE. Although an independent effect of AN on HE was not established in this study, we speculate that delayed intestinal transit secondary to AN may explain the higher incidence of HE in patients with AN.