OBJECTIVES Antibiotics are commonly classified into bactericidal and bacteriostatic agents based on their antimicrobial action. We aimed to assess whether this distinction is clinically relevant. METHODS OVID MEDLINE, EMBASE, The Cochrane Central Register of Controlled Trials (CENTRAL) and relevant references and conference proceedings using the Web of Science and Scopus databases were searched for randomized controlled trials comparing bactericidal with bacteriostatic antibiotics for treatment of severe infections. Main outcome measures were clinical cure rates and overall mortality. Abstracts of studies selected in the database search were screened by one reviewer; full-text screening and data extraction were performed by three independent reviewers. RESULTS Thirty-three studies were included. Approximately half of patients were treated with bacteriostatic monotherapy. Infections covered were pneumonia (n = 13), skin and soft tissue infections (n = 8), intra-abdominal infections (n = 4) and others (n = 8). Neither clinical cure rates [risk ratio (RR), 0.99; 95% CI, 0.97-1.01; P = 0.11] nor mortality rates (RR, 0.91; 95% CI, 0.76-1.08; P = 0.28) were different between patients treated with bactericidal drugs and those treated with bacteriostatic drugs. Subgroup analyses showed a benefit for clinical cure rates associated with linezolid and increased mortality associated with tigecycline. In meta-regression, clinical cure rates remained higher in patients treated with linezolid (P = 0.01); tigecycline displayed a close to significant association with increased mortality (P = 0.05) if compared with other bacteriostatic agents. CONCLUSIONS The categorization of antibiotics into bacteriostatic and bactericidal is unlikely to be relevant in clinical practice if used for abdominal infections, skin and soft tissue infections and pneumonia. Because we were not able to include studies on meningitis, endocarditis or neutropenia, no conclusion regarding these diseases can be drawn.