Hepatitis E virus (HEV) is viewed as an emerging pathogen. Many European countries, including Germany, have observed a steep increase of notified autochthonous hepatitis E cases in recent years. Our study investigated time trends in HEV seroprevalence in southern Germany between 2003 and 2015. A total of 3000 study sera were evenly distributed over sampling years 2003, 2006, 2009, 2012, and 2015, two age groups (20-29 and 30-39 years) and genders and were tested for anti-HEV IgG. Positive samples were quantified. The seroprevalence declined from 32.8% in 2003 over 22.5% in 2006 (p < 0.001) and 22.3% in 2009 to 17.7% and 17.8% in 2012 and 2015. A higher prevalence was found for males (p = 0.018) and the older age group (p < 0.001). Anti-HEV IgG concentrations ranged from 0.22 to 1783.19 WU mL(-1). A higher median concentration (2.41 vs. 1.89 WU mL(-1), p < 0.001) was found in the younger age group. The anti-HEV IgG seroprevalence decreased since 2003 and remains constant at similar to 18% since 2012. A rather low anti-HEV prevalence in young adults is indicative of a susceptible population and denotes a higher risk of HEV infections in this age group in the future. Therefore, reduction of HEV infection sources, close monitoring, and vigilance for proper control measures are warranted.