BackgroundThe treatment of complicated intra-abdominal infections remains a challenge. Both optimal medical and surgical therapy (i.e., source control) are needed to achieve low mortality and morbidity. The objective of this systematic review and meta-analysis is to determine the impact of carbapenem antibiotic therapy compared to other antibiotics in complicated intra-abdominal infections (secondary peritonitis) with an emphasis on mortality and postoperative complications.MethodsA systematic literature search from PubMed/Medline and Web of Science databases was carried out. The last search was conducted in August 2022. PRISMA guidelines were followed. Pre-defined outcomes were mortality, treatment success, treatment failure, and adverse events.ResultsTen randomized controlled trials, published from 1983 to 2013 with a total of 2377 patients (1255 patients in the carbapenem antibiotics group and 1122 in the control group), were identified. A meta-analysis comparing patients undergoing carbapenem antibiotic therapy and patients receiving other antibiotics was performed. No significant difference regarding mortality (OR 1.19, 95% CI [0.79; 1.82],p= 0.40), treatment success (OR 1.17, 95% CI [0.72; 1.91],p= 0.53), and treatment failure (OR 0.84, 95% CI [0.48; 1.45],p= 0.52) was observed. Carbapenem therapy was associated with fewer adverse events compared to therapy with other antibiotics (OR 0.79, 95% CI [0.65; 0.97],p= 0.022).ConclusionThere is currently no evidence that carbapenem antibiotics are superior in terms of mortality, and success or failure for the treatment of complicated intra-abdominal infections (secondary peritonitis). The rate of adverse events is lower under carbapenem therapy compared to control antibiotics.Trial RegistrationPROSPERO 2018 CRD42018108854.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11605-023-05651-7.