Background Few studies discuss causes and outcomes of peritonitis in low-income settings. This study describes epidemiology of patients with peritonitis at a Rwandan referral hospital. Identification of risk factors associated with mortality and unplanned reoperation could improve management of peritonitis. Methods Data were collected on demographics, clinical presentation, operative findings, and outcomes for all patients with peritonitis. Multivariate regression analysis identified factors associated with in-hospital mortality and unplanned reoperation. Results A total of 280 patients presented with peritonitis over a 6-month period. Causes of peritonitis were complications of intestinal obstruction (39%) and appendicitis (17%). Thirty-six (13%) patients required unplanned reoperation, and in-hospital mortality was 17%. Factors associated with increased odds of in-hospital mortality were unplanned reoperation (adjusted odds ratio 34.12), vasopressor use (adjusted odds ratio 24.91), abnormal white blood cell count (adjusted odds ratio 12.6), intensive care unit admission (adjusted odds ratio 9.06), and American Society of Anesthesiologist score ≥3 (adjusted odds ratio 7.80). Factors associated with increased odds of unplanned reoperation included typhoid perforation (adjusted odds ratio 5.92) and hypoxia on admission (adjusted odds ratio 3.82). Conclusion Peritonitis in Rwanda presents with high morbidity and mortality. Minimizing delays in care is important, as many patients with intestinal obstruction present with features of peritonitis. A better understanding of patient care and management prior to arrival at the referral hospital is needed to identify areas for improvement at the health center and district hospital.