<b><i>Introduction:</i></b> The efficacy of antibiotics for diverticulitis without abscess or peritonitis (uncomplicated diverticulitis) is controversial. We aimed to investigate the effectiveness of antibiotics for uncomplicated diverticulitis. <b><i>Methods:</i></b> We collected admission data for patients with acute uncomplicated diverticulitis using a nationwide database. We divided eligible admissions into two groups according to antibiotic initiation within 2 days after admission (antibiotic group vs. nonantibiotic group). We conducted propensity score matching and compared the rates of surgery (intestinal resection and stoma creation), in-hospital death, and medical costs between the groups. We also performed multivariate analysis to identify the clinical factors that affect surgery. <b><i>Results:</i></b> We enrolled 131,936 admissions; among these, we obtained 6,061 pairs after propensity score matching. Rates of both intestinal resection and stoma creation in the antibiotic group were lower than those in the nonantibiotic group (0.61 vs. 3.09%, <i>p</i> < 0.0001, and 0.08 vs. 0.26%, <i>p</i> = 0.027, respectively). Median costs in the antibiotic group were higher than those in the nonantibiotic group (315,820 JPY vs. 300,175 JPY, <i>p</i> < 0.0001, respectively). Multivariate analysis showed that non-initiation of antibiotics within 2 days after admission was a clinical factor that increased the risk of intestinal resection (odds ratio [OR] = 5.19, 95% confidence interval [CI]: 4.38–6.16, <i>p</i> < 0.0001) and stoma creation (OR = 2.68, 95% CI: 1.53–4.70, <i>p</i> = 0.0006). <b><i>Conclusion:</i></b> Our results indicated that antibiotics for uncomplicated diverticulitis expected to have moderate to severe disease activity may reduce the risk of intestinal resection and stoma creation. Further investigations are warranted.