The emergence and rapid spread of multidrug-resistant gram-positive bacteria has become a vital and serious medical problem. A literature search was conducted in PubMed, EMBASE, and Elsevier databases to identify relevant publications. To calculate the risk ratios (RRs) with 95% confidential intervals (CIs), a fixed- or random-effects model was applied based on the heterogeneity across studies. Five studies containing seven RCTs were included in this meta-analysis. Regarding cSSTIs, HAP, SAB, there was no statistically significant difference in the rate of clinical cure between telavancin and vancomycin or standard therapy in intention-to-treat population (ITT) (RR 1.01, 95% CI 0.97–1.05, P = 0.72; FEM) and clinically evaluable population (CE) (RR 1.01, 95% CI 0.98–1.04, P = 0.41; FEM). However, telavancin was more effective than vancomycin or standard therapy in MRSA eradication rate (RR 1.08, 95% CI 1.02–1.14, P = 0.009; FEM). Regarding the safety profile, no statistically significant differences were found in all-cause mortality (9.0% vs. 8.4%; RR 1.07, 95% CI 0.88–1.31, P = 0.49; FEM) and overall adverse events (77.0% vs. 72.3%; RR 1.08, 95% CI 0.98–1.20, P = 0.12; FEM) between telavancin and vancomycin or standard therapy. Pooled data from cSSTIs, HAP and SAB studies on telavancin indicated higher rates of adverse-event related withdrawals (7.7% vs. 5.4%; RR 1.43, 95% CI 1.12–1.83, P = 0.05; FEM) and creatinine elevation (10.0% vs. 5.1%; RR 1.95, 95% CI 1.53–2.48, P<0.00001; FEM)than vancomycin or standard therapy.Telavancin and vancomycin or standard therapy are equally effective for the treatment of cSSTIs, HAP and SAB, and telavancin might be an option for the treatment of difficult-to-treat serious infections caused by MRSA. However, telavancin is associated a higher incidence of creatinine elevation and adverse-event related withdrawals.