Background: Viruses can cause either meningitis or encephalitis. It is unclear why some people suffer from aseptic meningitis, and others acquire aseptic encephalitis when infected with the same viral pathogens. The aim of this study was to compare demographic and laboratory factors between patients with aseptic meningitis and encephalitis. Methods: The demographic and laboratory differences were analyzed according to age, sex, diabetes, hypertension, C-reactive protein in the blood, white blood cell and protein in the cerebrospinal fluid, and glucose ratio (cerebrospinal fluid/blood). Additionally, we analyzed the nation-wide differencesin age between the patients with aseptic meningitis and those with encephalitis in Korea. Results: The patients with aseptic encephalitis were older, more likely to have hypertension, and had higher levels of C-reactive protein than did the patients with aseptic meningitis. However, the numbers of white blood cells in the cerebrospinal fluid were significantly higher in the patients with meningitis than in the patients with encephalitis. Multivariable analysis revealed that age >49 years, hypertension and a C-reactive protein level >5.81 mg/dL were independent and significant variables in the prediction of aseptic encephalitis. Additionally, the patients with aseptic encephalitis were older than those with aseptic meningitis in the nation-wide Korean database. Conclusions: Older age, hypertension, and higher levels of C-reactive protein are useful factors for the prediction of aseptic encephalitis.