Background: Acute uncomplicated diverticulitis (AUD) is a common cause of acute abdominal pain. Recent guidelines advise selective use of antibiotics in AUD patients. This meta-analysis aimed to compare the effectiveness of no antibiotics vs antibiotics in AUD patients. Methods: This review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses to identify randomized controlled trials (RCTs) involving AUD patients which compared the use of antibiotics with no antibiotics. Pooled outcome data was calculated using random effects modeling with 95% confidence intervals (CIs). Results: 5 RCTs with 1934 AUD patients were included. 979 patients were managed without antibiotics (50.6%). Patients in the no antibiotic and antibiotic groups had comparable demographics (age, sex, and body mass index) and presenting features (temperature, pain score, and C-reactive protein levels). There was no significant difference in rates of complicated diverticulitis (OR:.61, 95% CI: 0.27-1.36, P =.23), abscess (OR:.51, 95% CI:.08-3.25, P =.47) or fistula (OR:.33, 95% CI:.03-3.15, P =.33) formation, perforation (OR:.98, 95% CI:.32-3.07, P =.98), recurrence (OR:.96, 95% CI:.66-1.41, P =.85), need for surgery (OR: 1.36, 95% CI:.47-3.95, P =.37), mortality (OR: 1.27, 95% CI:.14-11.76, P =.82), or length of stay (MD:.215, 95% CI: −.43-.73, P =.61) between the 2 groups. However, the likelihood of readmission was higher in the antibiotics group (OR: 2.13, 95% CI: 1.43-3.18, P =.0002). Conclusion: There is no significant difference in baseline characteristics, clinical presentation, and adverse health outcomes between AUD patients treated without antibiotics compared to with antibiotics. [ABSTRACT FROM AUTHOR]