objective. To assess Clostridium difficile infection (CDI)-related colectomy rates by CDI surveillance definitions and over time at multiple healthcare facilities. setting. Five university-affiliated acute care hospitals in the United States. design and methods. Cases of CDI and patients who underwent colectomy from July 2000 through June 2006 were identified from 5 US tertiary care centers. Monthly CDI-related colectomy rates were calculated as the number of CDI-related colectomies per 1,000 CDI cases, and cases were categorized according to recommended surveillance definitions. Logistic regression was performed to evaluate risk factors for CDI-related colectomy. results. In total, 8,569 cases of CDI were identified, and 75 patients underwent CDI-related colectomy. The overall colectomy rate was 8.7 per 1,000 CDI cases. The CDI-related colectomy rate ranged from 0 to 23 per 1,000 CDI episodes across hospitals. The colectomy rate for healthcare-facility-onset CDI was 4.3 per 1,000 CDI cases, and that for community-onset CDI was 16.5 per 1,000 CDI cases (P<.05). There were significantly more CDI-related colectomies at hospitals B and C (P<.05). conclusions. The overall CDI-related colectomy rate was low, and there was no significant change in the CDI-related colectomy rate over time. Onset of disease outside the study hospital was an independent risk factor for colectomy.