Objective To investigate the cost-effect of Vancomycin and Linezolid in the treatment of MRSA infection, providing practical basis for clinical drug use. Methods Patients admitted into our hospital duringfrom January 2014 to March 2016 were retrospectively analyzed. All cases of MRSA infection using Vancomycin or (and) Linezolid as antibiotic therapy were included in this study. The efficacy and pharmacogenomics of Linezolid and Vancomycin in treatment of MRSA were recorded. Results Incidence of renal function in linezolid Linezolid group was significantly lower than that in Vancomycin group (P < 0.05). Time duration of antibiotics usage in Vancomycin group were prolonged compared with linezolid Linezolid group [(7.04 ± 0.45) d vs (5.12 ± 0.47), P < 0.05]. Longer hospitalization stay was also identified in Vancomycin group compared with Linezolid group [(10.76 ± 0.53) d vs(8.06 ± 0.58) d, P < 0.05]. DUI of Vancomycin and Linezolid were both less than 1, while therapeutic effectiveness and cost-effectiveness ratio (C/E) of Linezolid was significantly higher than that in Vancomycin group (P < 0.05).Conclusion Linezolid may be a better choice for treatment of MRSA due to better cost-effectiveness, efficacy and safety compared with Vancomycin.