Meconium ileus (MI) affects 15% of neonates with cystic fibrosis (CF). The authors reviewed the management and outcome of 51 neonates presenting to a single institution between 1976 and 1995 with MI secondary to CF. Clinical presentation included abdominal distension (96%), bilious vomiting (49%), and delayed passage of meconium (36%). A family history of CF was present in 4 cases (8%). Twenty-three neonates presented with MI and evidence of volvulus, atresia, or perforation (complicated MI). Of these, 16 underwent stoma formation, 1 appendicectomy, and 6 resection with primary anastomosis. Twenty-eight neonates presented with uncomplicated MI. Of these, 11 were managed non-operatively by Gastrografin enema (10) or enteral N-acetylcysteine (1). The remainder required stoma formation (15) or bowel resection with primary anastomosis (2). Early postoperative complications occurred in 2 neonates (4%). In this hospital the 1-year survival for this condition has increased from 49% (1953–1970) to 98% (1976–1995) irrespective of the surgical procedure performed or the presence of volvulus, atresia, or perforation. In our experience, bowel resection with primary anastomosis is as safe as stoma formation and is associated with a reduced length of initial hospital stay.