<b><i>Background:</i></b> The effectiveness of prophylactic antibiotics in severe acute pancreatitis (SAP) remains a debatable issue. This meta-analysis aimed to determine the efficacy of prophylactic carbapenem antibiotics in SAP. <b><i>Methods:</i></b> This meta-analysis of prophylactic carbapenem antibiotics for SAP was conducted in PubMed, EMBASE, Web of Science, MEDLINE, and Cochrane Library up to February 2021. The related bibliographies were manually searched. The primary outcomes involved infected pancreatic or peripancreatic necrosis, mortality, complications, infections, and organ failure. <b><i>Results:</i></b> Seven articles comprised 5 randomized controlled trials and 2 retrospective observational studies, including 3,864 SAP participants. Prophylactic carbapenem antibiotics in SAP were associated with a statistically significant reduction in the incidence of infections (odds ratio [OR]: 0.27; <i>p</i> = 0.03) and complications (OR: 0.48; <i>p</i> = 0.009). Nevertheless, no statistically significant difference was demonstrated in the incidence of infected pancreatic or peripancreatic necrosis (OR: 0.74; <i>p</i> = 0.24), mortality (OR: 0.69; <i>p</i> = 0.17), extrapancreatic infection (OR: 0.64, <i>p</i> = 0.54), pulmonary infection (OR: 1.23; <i>p</i> = 0.69), blood infection (OR: 0.60; <i>p</i> = 0.35), urinary tract infection (OR: 0.97; <i>p</i> = 0.97), pancreatic pseudocyst (OR: 0.59; <i>p</i> = 0.28), fluid collection (OR: 0.91; <i>p</i> = 0.76), organ failure (OR: 0.63; <i>p</i> = 0.19), acute respiratory distress syndrome (OR: 0.80; <i>p</i> = 0.61), surgical intervention (OR: 0.97; <i>p</i> = 0.93), dialysis (OR: 2.34; <i>p</i> = 0.57), use of respirator or ventilator (OR: 1.90; <i>p</i> = 0.40), intensive care unit treatment (OR: 2.97; <i>p</i> = 0.18), and additional antibiotics (OR: 0.59; <i>p</i> = 0.28) between the experimental and control groups. <b><i>Conclusions:</i></b> It is not recommended to administer routine prophylactic carbapenem antibiotics in SAP.