Cystic fibrosis (CF) is the most common life-shortening hereditary disease affecting the white population. Respiratory complications are the greatest determinant of adult survival, but gastrointestinal manifestations result in significant morbidity. Distal intestinal obstructive syndrome (DIOS) describes partial or complete intestinal obstruction in patients with CF beyond the neonatal period and is characterized by abnormally viscid mucofeculent material in the terminal ileum and ascending colon. The medical management of DIOS has been described; however, the optimal surgical strategy for this condition is unknown. Herein, we present a surgical case series and review the therapeutic surgical options. Distal intestinal obstructive syndrome will become an increasingly common complication in the adult with CF who may require operative therapy. Surgeons should have a high index of suspicion for DIOS in patients with CF and the symptoms of small-bowel obstruction.