Hyperamylasemia of greater than five times the upper limit of the normal range (200 IU/L) is highly specific for the diagnosis of pancreatitis, but the meaning of lower values is unclear. The purpose of this study was to evaluate the prognostic significance of amylase values > 200 and < 1000 IU/L. A controlled historical cohort study was conducted to determine whether moderate hyperamylasemia is associated with an increased severity of outcome compared to patients with normal amylase values. Subjects met certain inclusion criteria and had a serum amylase of > 200 and < 1000 IU/L (normal < 200 IU/L). The case group consisted of 44 patients (medium serum amylase = 307.5 IU/L) and resembled the control group of 77 patients (median serum amylase = 117.5 IU/L) with regard to sex distribution and presenting complaint. However, the case group was older, was on more medications, and had a shorter duration of symptoms prior to the ED visit (< 72 h). Analysis of clinically important outcomes revealed that the groups were similar in terms of 6-month mortality, general admission rate, ICU admission rate, and rate of surgical intervention. The proportion of patients who had radiologically or endoscopically documented gastrointestinal pathology was also similar. The results demonstrate that patients with moderate hyperamylasemia (i.e. amylase < 1000 IU/L), notwithstanding the fact that they are older, are on more medications, and have more acute symptomatology, did not have a worse outcome than patients with the same complaints and normal amylases.