Hemorrhagic fever with renal syndrome (HFRS) is a major rodent-borne zoonosis. Each year worldwide, 60,000-100,000 HFRS human cases are reported in more than seventy countries with almost 90% these cases occurring in China. Shaanxi Province in China has been among the most seriously affected areas since 1955. During 2009-2013, Shaanxi reported 11,400 human cases, the most of all provinces in China. Furthermore, the epidemiological features of HFRS have changed over time. Using long-term data of HFRS from 2005 to 2016, we carried out this retrospective epidemiological study combining ecological assessment models in Shaanxi. We found the majority of HFRS cases were male farmers who acquired infection in Guanzhong Plain, but the geographic extent of the epidemic has slowly spread northward. The highest age-specific attack rate since 2011 was among people aged 60-74 years, and the percentage of HFRS cases among the elderly increased from 12% in 2005 to 25% in 2016. We highly recommend expanding HFRS vaccination to people older than 60 years to better protect against the disease. Multivariate analysis revealed artificial area, cropland, pig and population density, GDP, and climate conditions (relative humidity, precipitation, and wind speed) as significant risk factors in the distribution of HFRS.