Although hyperamylasemia has been reported in a large proportion of patients undergoing cardiac surgery with cardiopulmonary bypass, its clinical significance and pathogenetic mechanisms remain poorly understood. The study was designed to investigate whether avoidance of cardiopulmonary bypass would limit amylase elevation. Serum levels of amylase and lipase were measured preoperatively as well as 24 and 48 hours postoperatively in 58 patients undergoing elective coronary artery bypass grafting. Three surgical approaches were used: cardiopulmonary bypass (n = 32) and off-pump through a median sternotomy (n = 14) or a left minithoracotomy (n = 12). There was no hospital mortality or postoperative abdominal complications. Transient hyperamylasemia occurred in 14 patients: 7 (22%), 5 (36%), and 2 (17%) in the respective groups. The increase in amylase levels was similar among the groups. However, no lipase elevation was detected in any patient. There was no clear correlation between hyperamylasemia and increased creatinine levels. Perioperative plasma calcium levels were normal in patients who had hyperamylasemia. Our results indicate that hyperamylasemia after bypass surgery is not related to the use of cardiopulmonary bypass or the mode of surgical access.