OBJECTIVES: Vancomycin and linezolid are amongst the most commonly prescribed antibiotics for hospital-acquired infections in China. The aim of this study is to estimate and compare the baseline characteristics, hospitalization costs, length of stay (LOS), length of therapy (LOT) and all-cause in-hospital mortality of patients treated with vancomycin or linezolid. METHODS: Data were extracted from the electronic medical records (EMR) of a tertiary hospital in Shanghai (bed size 1700). The analysis included patients admitted for any underlying cause who received either vancomycin or linezolid between January 2009 and July 2012. Continuous variables were compared with t test and chi-square for categorical variables. RESULTS: Of the total 3234 patients identified, 93.6% were treated with vancomycin (female: 40.6%, mean age: 55.8 years) and 6.4% were treated with linezolid (female: 22.2%, mean age: 62.3 years). Cardiac Surgery was the most frequent admitting department for the both groups, while cardiovascular disease was the top admission reason for the vancomycin group and pulmonary infection for the linezolid group. The average daily dose was 1.6±1.1 g for vancomycin and 1.2±0.5 g for linezolid. The all-cause in-hospital mortality was lower in the vancomycin group compared to the linezolid group (4.2% vs. 21.7%, p<0.001). The vancomycin group had shorter LOS and LOT compared to the linezolid group (23.6±24.4 vs. 37.1±40.8 days, p<0.001; 7.0±8.8 vs. 8.7±10.6 days, p=0.025). The vancomycin group had lower total hospitalization costs, medication costs and antibiotics costs compared to the linezolid group (RMB 68788±64956 vs. 125425±117055, p<0.001; 33258±39792 vs. 70372±69115, p<0.001; 15206±18957 vs. 34681±33184, p<0.001).  CONCLUSIONS: Vancomycin was more frequently prescribed than linezolid and was more likely to be used in females and younger patients. When compared to those patients treated with linezolid, vancomycin treatment was associated with a shorter LOS and LOT, decreased total hospitalization costs and decreased total medication and antibiotics costs.