Recent studies have evaluated outcomes associated with duration of antimicrobial treatment for complicated intra-abdominal infections (cIAI). The goal of this guideline was to help clinicians better define appropriate antimicrobial duration in patients who have undergone definitive source control for cIAI. A working group of Eastern Association for the Surgery of Trauma (EAST) performed a systematic review and meta-analyses of the available data pertaining to the duration of antibiotics after definitive source control of cIAI in adult patients. Only studies that compared patients treated with short vs. long duration antibiotic regimens were included. The critical outcomes of interest were selected by the group. Noninferiority of short compared with long duration of antimicrobial treatment was defined as an indicator for a potential recommendation in favor of shorter antibiotics course. The Grading of Recommendations Assessment, Development and Evaluation methodology was used to assess the quality of the evidence and to formulate recommendations. Sixteen studies were included. The short duration ranged from 1 dose to ≤10 days, with an average of 4 days, and the long duration ranged >1 day to 28 days, with an average of 8 days. There were no differences between short and long duration of antibiotics in terms of mortality (odds ratio [OR], 0.90; 95% confidence interval [CI], 0.56-1.44), rate of surgical site infection (OR, 0.88; 95% CI, 0.56-1.38); persistent/recurrent abscess (OR, 0.76; 95% CI, 0.45-1.29); unplanned interventions (OR, 0.53; 95% CI, 0.12-2.26); hospital length of stay (mean difference, -2.62 days; CI, -7.08 to 1.83 days); or readmissions (OR, 0.92; 95% CI, 0.50-1.69). The level of evidence was assessed as very low. The group made a recommendation for shorter (four or less days) versus longer duration (eight or more days) of antimicrobial treatment in adult patients with cIAIs who had definitive source control.