The clinical outcome of acute pancreatitis complicating acute exacerbation of chronic hepatitis virus B (HBV) infection has never been studied. Ninety patients with acute pancreatitis were recruited. Five patients (5.6%) (Group 1) had acute pancreatitis superimposed on acute exacerbation of chronic HBV infection with no other causes of acute pancreatitis being identified. The clinical outcome of these five patients was compared to the 85 non-HBV infected patients (Group 2) with acute pancreatitis. A third group (Group 3) of patients (n=406) with acute exacerbation of chronic HBV infections without acute pancreatitis was also recruited for comparison. Group 1 had a significantly higher mortality rate (4 out of 5, 80%) compared to those of Group 2 (13 out of 85, 15.3%, P=0.0041) and Group 3 (9 out of 406, 2.2%, P < 0.0001). In Group 1 patients, the acute pancreatitis occurred during the initial rise of HBV DNA with relatively low or normal level of alanine aminotransferase (ALT) in two patients, during the rise of ALT with declining level of HBV DNA in one patient, and during the cholestatic phase of the acute exacerbation in one patient. The acute pancreatitis was clinically silent and only diagnosed by computerized tomography in the remaining patient. Direct viral damage and/or immunological attack to the pancreatic tissue were probably the underlying pathogenesis of the acute pancreatitis in these patients. In conclusion, acute pancreatitis complicating acute exacerbation of chronic HBV infection carried an extremely poor prognosis with high mortality.