Although the natural history of H1N1 has been found to vary among patients, little is known about the factors that affect these variations. Infected patients with an extended infection history may shed virus longer and spread infection. To further clarify these variations, we evaluated the natural history of H1N1 infection in 324 university students using a descriptive epidemiological method and analyzed factors affecting the natural history of infection. The median times from infection to fever development and from fever development to cure were 2 days (range 0?8 days) and 5 days (range 1?12 days), respectively, and the median time not attending classes was 5 days (range, 1?13 days). Variations in H1N1 natural history were associated with both environmental and individual factors, including route of infection, grade, gender, epidemic period, respiratory and gastrointestinal symptoms and headache. Steps affecting these factors may help control variations in H1N1 natural history and may enhance infection control measures.