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Background: While the rate of negative appendectomy seems to be decreasing in the era of multi-slice helical computed tomography (CT scans), controversy still exists regarding the necessity of CT scan in the diagnosis of acute appendicitis. We sought to determine the role of CT scan in accurately diagnosing acute appendicitis.Methods: This retrospective, IRB-approved, HIPAA-compliant study was performed in a 746-bed tertiary care urban academic hospital with 65000 annual emergency department visits. Informed consent was waived and the medical records system was used to identify all patients age 18-80 years who underwent a non-incidental appendectomy during the 6-year period after the introduction of multi-slice helical CT scanners to our institution. These patients were correlated with the ICD-9 code for acute appendicitis, and the radiology database was used to identify which patients underwent CT scan within one week of admission. Chi squared analysis was used to assess for significant differences in proportions, and a p value of 0.05 was considered significant.Results: From April 2004 to April 2010, 510 patients meeting our criteria underwent non-incidental appendectomies. 427 (83.7%) of these patients underwent CT scan within one week of admission. The overall negative appendectomy rate was 11.6%. In patients who underwent CT scan, the negative appendectomy rate was 5.6%, whereas the negative appendectomy rate was 42.2% in patients who did not get a CT scan (p<0.001). In males, the negative appendectomy with and without CT scan was 2.3% and 24.0% respectively (p<0.001). In females, the negative appendectomy rates were 9.2% and 50.0% with and without CT scan respectively (p<0.001).Conclusion: CT scan significantly reduces the rate of negative appendectomy in both males and females.