We determined whether telavancin is as active in experimental immunocompetent murine pneumococcal pneumonia as is vancomycin or ceftriaxone. Experimental murine pneumonia was established by intratracheal administration of Streptococcus pneumoniae. Four groups of animals were studied, untreated and treated with vancomycin (110 mg/kg, bid, SQ), telavancin (40 mg/kg, bid, SQ), or ceftriaxone (50 mg/kg, bid, SQ) for 2 days. The untreated animals had a mean of 6.54 ± 0.82 log10 cfu/g lung. The vancomycin-, telavancin-, and ceftriaxone-treated animals had means of 2.01 ± 0.02, 2.00 ± 0.00, and 2.00 ± 0.01 log10 cfu/g lung, respectively (p-values < 0.0001 for each treatment group versus the untreated group). In the model studied, telavancin was as active as vancomycin and ceftriaxone in treating experimental pneumococcal pneumonia in mice.