Beyond infancy, pneumatosis cystoides intestinalis (PCI) is rare. Data concerning pathogenesis and treatment are limited. Our experience with 12 children was examined to define predisposing factors, presentation, treatment, and outcome. Nine children were immunosuppressed, thus identifying an important etiologic subgroup. Presentation was variable but included abdominal pain, distention, diarrhea and hematochezia. Clostridium difficile was found in 3 patients and cytomegalovirus in 1. Radiographs showed free air in 3. Nine were treated with antibiotics and bowel rest, 1 with bowel rest alone, 1 with oral metronidazole, and 1 with observation. PCI resolved in 7 of 9 treated with antibiotics, although 1 child with leukemia had severe hematochezia secondary to colonic ulceration and required hemicolectomy. No other patient required laparotomy. The free air resolved in 2 of 3. There were 2 deaths, both from sepsis. One had free air on admission but no perforation was found at autopsy. Treatment recommendations remain unclear; however, C difficile and cytomegalovirus are important pathogens that should be identified and treated promptly. In symptomatic patients, bowel rest and antibiotics seem beneficial. Operative intervention should be reserved for patients with peritoneal signs, progressive deterioration, obstruction, or persistent, severe bleeding. Free air alone is not an indication for operative management in children with PCI.