Linezolid has been approved for the treatment of patients with infections caused by Gram-positive cocci that are resistant to traditionally used antibiotics, including glycopeptides. This oxazolidinone antibiotic has been reported to have excellent pharmacokinetics and effectiveness. We did a meta-analysis of randomised controlled trials (RCTs) to clarify whether linezolid is superior to glycopeptides or beta-lactams for the treatment of Gram-positive infections. 12 RCTs, involving 6093 patients, were included. Overall, with respect to treatment success, linezolid was more effective than glycopeptides or beta-lactams (odds ratio [OR] 1.41 [95% CI 1.11-1.81]). Mortality was similar between the groups (OR 0.97 [0.79-1.19]). Linezolid was more effective than comparators in patients with skin and soft-tissue infections (OR 1.67 [1.31-2.12]) and bacteraemia (OR 2.07 [1.13-3.78]). However, there was no difference in treatment success for patients with pneumonia (OR 1.03 [0.75-1.42]). Treatment with linezolid was not associated with more adverse effects in general (OR 1.40 [0.95-2.06]); however, thrombocytopenia was recorded more commonly in patients receiving linezolid (OR 11.72 [3.66-37.57]). Although linezolid is more effective than its comparators for the empirical treatment of selected patients, several points, such as the use of less potent antistaphylococcal beta-lactams, the same all-cause mortality, and the higher probability of thrombocytopenia, should be taken into account and may limit the use of linezolid to specific patient populations or infections that are difficult to treat with other antibiotics.