OBJECTIVE: The overall mortality for patients undergoing surgery for perforated peptic ulcer has increased despite improvements in perioperative monitoring and treatment. The objective of this study was to identify and describe perioperative risk factors in order to identify ways of optimizing the treatment and to improve the outcome of patients with perforated peptic ulcer. MATERIAL AND METHODS: Three hundred and ninety-eight patients undergoing emergency surgery in four university hospitals in Denmark were included in the study. Information regarding the pre-, intra- and postoperative phases were recorded retrospectively from medical records. Data were analysed using multiple logistic regression analysis. The primary end-point was 30-day mortality. RESULTS: The 30-day mortality rate was 27%. The following variables were independently associated with death within 30 days of surgery: ASA (American Society of Anaesthesiologists) class, age, shock upon admission, preoperative metabolic acidosis, elevated concentration of creatinine upon admission, subnormal concentration of albumin upon admission and insufficient postoperative nutrition. CONCLUSIONS: Thus, preoperative metabolic acidosis, renal insufficiency upon admission and insufficient postoperative nutrition have been added to the list of independent risk factors for death within 30 days of surgery in patients with peptic ulcer perforation. Finding that shock upon admission, reduced albumin blood levels upon admission, renal insufficiency upon admission and preoperative metabolic acidosis are independently related to 30-day mortality could indicate that patients with peptic ulcer perforation are septic upon admission, and thus might benefit from a perioperative care protocol with early source control and early goal-directed therapy according to The Surviving Sepsis Campaign. This hypothesis should be addressed in future studies.