BACKGROUND: The objective of our analysis was to determine the optimal timing of cholecystectomy during admission for acute cholecystitis. METHODS: All patients from the American College of Surgeons National Surgical Quality Improvement Program Participant User Files from 2005 through 2010 who underwent emergency cholecystectomy within 7 days of hospital admission for acute cholecystitis were included for analysis. The association between timing of cholecystectomy and postoperative outcomes was determined using multivariate logistic regression analyses after adjustment for patient demographics, acute and chronic comorbid medical conditions, preoperative sepsis classification, American Society of Anesthesiologists physical status classification, and preoperative liver function tests. RESULTS: A total of 5,268 patients were included for analysis. The timing of operation was day of admission for 49.7% of these patients, 1 day after admission for 33.4%, 2 days after admission for 9.5%, 3 days after admission for 3.9%, and 4 days to 7 days after admission for 3.6%. Multivariate logistic regression analyses revealed no significant association between timing of operation and 30-day postoperative mortality or overall morbidity. Patients who underwent operation later in the course of admission were more likely to require an open procedure and sustained significantly longer postoperative and overall lengths of hospitalization. Similar findings were demonstrated for a subgroup of patients who exhibited characteristics that placed them at higher risk for surgical intervention. CONCLUSION: Immediate cholecystectomy is preferred for patients who require hospitalization for acute cholecystitis. LEVEL OF EVIDENCE: Economic/decision analysis, level III.