Background and Aims Recently, epidemiology studies of hepatitis E in different areas are attracted more attention. Extensive studies of prevalent status and clinical manifestations could help us to broaden our knowledge, so as to excellently prevent and treat hepatitis E. The study analyzed the epidemiological characteristics and clinical features of 394 cases of sporadic acute hepatitis E (AHE) in Southwest of China from 2008 to 2010. Methods The clinical data of 394 cases with sporadic AHE in Southwest of China from 2008 to 2010 were reviewed. Results In the 394 cases with sporadic AHE, the ratio of male/female was 1.432∶1, and the mean age was (31.53 ± 18.12) years. Totally, 94 (23.86%) patients aged under 18, 271 (68.78%) patients aged between 18 and 60, and 29 (7.36%) patients aged above 60. The incidence rate was signiifcantly increased in summer (P = 0.000), especially in May (14.72%) and July (13.71%). In addition, the characteristics of occupation and ethnic group distribution were migrant laborers (106/394, 26.90%) and Han people (365/394, 92.64%). The length of stay, incidence of jaundice, the peak value of total bilirubin and alanine aminotransferase in male patients were all higher than those in female patients signiifcantly (P < 0.05). The prolonged length of stay, decreased levels of ALT/ALB/CHE, increased levels of TBil, and increased incidence of jaundice and fatigue were associated with older age signiifcantly (P < 0.05). The differences in peak values of total bilirubin (TBil), total bile acid (TBA), glutamyltransferase (GGT), cholinesterase (CHE) between AHE group and the groups of AHE accompanied respectively by chronic hepatitis B (CHB), acute alcoholic fatty liver (AFL), nonalcoholic fatty liver disease (NAFLD) were signiifcant (P<0.05). In addition, no signiifcant difference was found in length of stay and biochemical indexes among anti-HEV-IgG positive group, anti-HEV-IgM positive group and anti-HEV-IgM/IgG both positive group (P>0.05). Conclusions Four epidemiological characteristics, including aged between 18 and 60, male, summer and migrant laborers, are found to be associated with acute hepatitis E. The prognosis of AHE in the majority of patients was favorable, but aged above 60 years and coexistence with CHB, AFL and NAFLD could be considerede as the factors inducing the infaust prognosis.