Abstract: Introduction: Peritonitis is a life-threatening condition with a multitude of etiologies that can vary with geographic location. The aims of this study were to elucidate the etiology, clinical presentation and outcomes associated with peritonitis in Lilongwe, Malawi. Methods: All patients admitted to Kamuzu Central Hospital (KCH) who underwent an operation for treatment of peritonitis during the calendar year 2008 were eligible. Peritonitis was defined as abdominal rigidity, rebound tenderness, and/or guarding in one or more abdominal quadrants. Subjects were identified from a review of the medical records for all patients admitted to the adult general surgical ward and the operative log book. Those who met the definition of peritonitis and underwent celiotomy were included. Results: 190 subjects were identified. The most common etiologies were appendicitis (22%), intestinal volvulus (17%), perforated peptic ulcer (11%) and small bowel perforation (11%). The overall mortality rate associated with peritonitis was 15%, with the highest mortality rates observed in solid organ rupture (35%), perforated peptic ulcer (33%), primary/idiopathic peritonitis (27%), tubo-ovarian abscess (20%) and small bowel perforation (15%). Factors associated with death included abdominal rigidity, generalized (versus localized) peritonitis, hypotension, tachycardia and anemia (p < 0.05). Age, gender, symptoms (obstipation, vomiting) and symptom duration, tachypnea, abnormal temperature, leukocytosis, hemoconcentration, thrombocytopenia and thrombocytosis were not associated with mortality (p = NS). Conclusions: There are several signs and laboratory findings predictive of poor outcome in Malawian patients with peritonitis. Tachycardia, hypotension, anemia, abdominal rigidity and generalized peritonitis are the most predictive of death (P < 0.05 for each). Similar to studies from other African countries, in our population the most common cause of peritonitis was appendicitis, and the overall mortality rate among all patients with peritonitis was 15%. Identified geographical differences included intestinal volvulus, rare in the US but the 2nd most common cause of peritonitis in Malawi and gallbladder disease, common in Ethiopia but not observed in Malawi. Future research should investigate whether correction of factors associated with mortality might improve outcomes.