This invention provides methods of determining the risk of AP development in an individual, as well as the diagnosis, prognosis, and treatment of acute pancreatitis (AP) in an individual, by determining the presence or absence of significantly high levels of free serum DNA in the subject relative to levels in a healthy individual. In other embodiments, the invention further provides methods of determining the risk of severe AP development, prognosis, diagnosis, and treatment of a severe form of acute pancreatitis based upon the presence of significantly high levels of free serum DNA in the subject relative to an individual who has and maintains a mild form of acute pancreatitis.