Acute mesenteric ischemia (AMI) is a catastrophic surgical condition, especially in older patients with multiple comorbidities. The aim of this study was to evaluate the impact of comorbidity on perioperative mortality and overall survival in patients surgically treated for AMI. A series of 186 consecutive patients (106 men and 80 women) who underwent surgery because of AMI in a university tertiary care center between 1990 and 2006 were retrospectively studied. The Charlson Comorbidity Index (CCI) score, unadjusted and adjusted by age, was preoperatively calculated in each patient. Perioperative mortality and overall survival were also recorded. The association between unadjusted and adjusted by age CCI and perioperative mortality and overall survival were analyzed. The mean age of the studied population was 72.1 years (SE +/-13.7 years). Hospital mortality was 64.5%. One-year, 3-year, and 5-year overall estimated survival by the Kaplan-Meier method after surgery for AMI was 26%, 23% and 21%, respectively. Perioperative mortality was not related to the unadjusted preoperative CCI (p = 0.093). Nevertheless, a statistically significant association was found between mortality and preoperative adjusted CCI (p = 0.007). Likewise, CCI unadjusted was almost related to overall survival (p = 0.055), but the values of the categorized CCI adjusted by age showed a statistically significant difference in overall survival (p = 0.012). In multivariate analysis, CCI adjusted by age remained independent prognostic factor of mortality. Comorbidity adjusted by age may play a role as a predictive factor for perioperative mortality and long-term survival in patients operated on for AMI.