Antibiotic treatment is the standard care for patients with uncomplicated acute diverticulitis. However, this practice is based on low-level evidence and has been challenged by findings from 2 randomized trials, which did not include a placebo group. We investigated the non-inferiority of placebo vs antibiotic treatment for the management of uncomplicated acute diverticulitis.In the selective treatment with antibiotics for non-complicated diverticulitis study, 180 patients hospitalized for uncomplicated acute diverticulitis (determined by computed tomography, Hinchey 1a grade) from New Zealand and Australia were randomly assigned to groups given antibiotics (n = 85) or placebo (n = 95) for 7 days. We collected demographic, clinical, and laboratory data and answers to questionnaires completed every 12 hrs for the first 48 hrs and then daily until hospital discharge. The primary endpoint was length of hospital stay; secondary endpoints included occurrence of adverse events, readmission to the hospital, procedural intervention, change in serum markers of inflammation, and patient-reported pain scores at 12 and 24 hrs.There was no significant difference in median time of hospital stay between the antibiotic group (40.0 hrs; 95% CI, 24.4-57.6 hrs) and the placebo group (45.8 hrs; 95% CI, 26.5-60.2 hrs) (P=.2). There were no significant differences between groups in adverse events (12% for both groups; P=1.0), readmission to the hospital within 1 week (6% for the placebo group vs 1% for the antibiotic group; P=.1), and readmission to the hospital within 30 days (6% for the placebo group vs 11% for the antibiotic group; P= .3).Foregoing antibiotic treatment did not prolong length of hospital admission. This result provides strong evidence for omission of antibiotics for selected patients with uncomplicated acute diverticulitis.