Objectives (1) To obtain a literature review concerning pathogenesis and incidence of stress ulceration (SU) in patients undergoing cardiac surgery. (2) To determine which methods are useful in the prevention of SU and to analyze whether SU prophylaxis by acid reduction is effective in patients undergoing cardiac surgery.Design Literature review from Medline and reference list of identified articles until 1999.Measurements and Main Results SU and upper gastrointestinal bleeding (UGIB) in patients after cardiac surgery have been reported since 1957. All articles were retrospective reports. Definitions of SU and UGIB were variable. Ischemia, reperfusion injury, and endotoxemia were the main pathogenetic mechanisms in SU formation. Valve replacement, aortic cross-clamping and bypass time, nonpulsatile flow during bypass, reoperation, and inflammatory state were risk factors for UGIB. Randomized, controlled clinical trials concerning SU prophylaxis have not been performed. The overall incidence of UGIB was 0.45% (638 bleeds in 141,887 patients). In patients with known use of SU prophylaxis with histamine2-receptor antagonists or antacids, the incidence of UGIB was 0.35%, and in patients without these medications, the incidence of UGIB was 0.45% (p = 0.16).Conclusions Pathogenesis and risk factors for SU and UGIB are summarized. A review of the literature showed that the incidence of UGIB in patients after cardiac surgery was low. A randomized, controlled trial concerning pharmacologic stress ulcer prophylaxis has not been performed. The available retrospective reports concerning pharmacologic stress ulcer prophylaxis do not support the routine use of histamine2-receptor antagonists.