Pneumatosis intestinalis (PI) occurs in a wide variety of patients, some of whom require urgent surgery, while others can be observed with resolution of symptoms and radiographic findings. During 1 year, 27 patients with PI were prospectively evaluated for clinical, laboratory, and radiographic features that would be useful in predicting the need for surgery, the pathologic findings, and patient outcome. Sixteen of the twenty-seven patients underwent laparotomy, with only one negative exploration. Of the 11 patients not explored, there were two deaths in moribund patients. Seven of nine patients with jejunostomy tubes, recent gastrointestinal anastomoses, inflammatory bowel disease, lactulose therapy, or chemotherapy who did not have clinical evidence of an acute surgical abdomen or metabolic acidosis survived without surgery (two deaths unrelated to the gastrointestinal tract). Patients presenting with bowel obstruction and PI required surgery in seven of nine cases, did not have necrotic bowel, and had 11% mortality. Eight patients with ischemic bowel had a 75% mortality rate, despite surgery. Patients with PI and clinical evidence of bowel obstruction or ischemia usually require urgent surgery, while asymptomatic patients without metabolic acidosis can be safely observed.