It was recently demonstrated in experimental models that, after pancreatic outflow obstruction, serum amylase levels first increase and then progressively decline regardless of whether the obstruction was maintained or relieved. Furthermore, early decompression of the ductal biliary system may prevent the progression of the disease. This finding prompted us to look for a similar pattern in patients with obstructive acute pancreatitis due to biliary stones. Forty-two patients with biliary acute pancreatitis were prospectively studied. Twenty-one patients underwent urgent endoscopic sphincterotomy (ES), and 21 received conservative medical treatment (CMT). The two groups were comparable for sex, age, onset of pain, and seventy. Serum amylase and lipase were determined in all patients on admission and 24 h later. The percentage variation of serum amylase and lipase was calculated considering, for each patient, the concentrations of the two enzymes assayed on admission and 24 h later. On admission, all patients had elevated serum concentrations of amylase (mean ± SEM: ES, 2,560 ± 473 UL; CMT, 1,783 ± 481 U/L) and lipase (ES, 3,037 ± 574 U/L; CMT, 3,179 ± 724 U/L). The serum amylase variation (mean ± SEM) was −65.6 ± 5.5% in the ES and −47.2.1 ± 8.1% in the CMT patients. The serum lipase variation was −59.1 ± 7.7 and −33.1 ± 18% in the same groups, respectively. These differences were not statistically significant. Acute pancreatitis worsened in one patient in the ES group and in seven in the CMT group; this difference was statistically significant (p <0.02). The mean length of hospitalization was 8.9 days in the ES group and 19.7 days in the CMT group (p <0.001). Serum pancreatic enzymes determination is not useful to evaluate the results of the early decompression of biliary duct in human acute pancreatitis. Indeed, early endoscopic sphincterotomy may result in a substantial improvement in the outcome of biliary acute pancreatitis.