OBJECTIVE To compare the effectiveness of meropenem with imipenem plus cilastatin in the treatment of severe infections. METHODS CENTRAL, EMBASE and MEDLINE were searched for abstracts and papers. All searching was completed in March 2004. No restriction was placed on language. METHODS Randomized controlled trials of adult patients with severe infections treated with meropenem or imipenem plus cilastatin at an equal dose, on a gram-for-gram basis, and with the same dosing regimen. METHODS Two reviewers independently assessed papers against the inclusion/exclusion criteria and for methodological quality with differences in opinion adjudicated by a third party. Data were extracted on clinical response, bacteriologic response, mortality and adverse events. RESULTS A total of 27 trials met the inclusion criteria. Meta-analyses were carried out using a Fixed Effects model. Results demonstrated that when compared to imipenem plus cilastatin, meropenem is associated with a significantly greater clinical response (Relative Risk 1.04; 95% Confidence Interval: 1.01-1.06), a significantly greater bacteriologic response (RR 1.05; 95% CI: 1.01-1.08), a non-significant reduction in mortality (RR 0.98; 95% CI: 0.71-1.35), and a significantly lower adverse event rate (RR 0.87; 95% CI: 0.77-0.97). CONCLUSIONS This systematic review demonstrates that meropenem compared to imipenem plus cilastatin has a significantly greater clinical and bacteriologic response with a significant reduction in adverse events. There was no evidence of heterogeneity or publication bias and the analyses were robust to changes in the inclusion/exclusion criteria and use of a Random Effects model.