Patients on systemic steroid therapy are at increased risk of diffuse peritonitis, specially from gastrointestinal perforation. We performed a retrospective study of 37 patients on systemic steroid therapy who underwent surgery for diffuse peritonitis. Clinical presentation of peritonitis was usually aspecific, making the diagnosis difficult. The median interval between onset of symptoms and surgery was 3.3 days, reduced to 2.0 days between hospitalization and surgery. The mortality rate was 46% (17 of 37 patients). We emphasize aggressive diagnostic efforts and early abdominal exploration in front of any persisting abdominal pain in patients on systemic steroid therapy.