Objective To retrospectively analyze the changing trend of minimum inhibitory concentration (MIC) of vancomycin against methicillin-resistant Staphylococcus aureus (MRSA), provide reference for the clinical use of vancomycin in the treatment of MRSA infection. Methods 900 strains of non-repetitive MRSA from clinical specimens in 3 tertiary first-class general hospitals in Xuzhou City in 2015-2019 were selected according to the standard of healthcare-associated infection (HAI), MIC values were collected, MICs of vancomycin to MRSA between intensive care units (ICUs) and non-ICUs were compared, and related characteristics were analyzed. Results 900 strains of MRSA were all sensitive to vancomycin, the mean MIC values in 2015-2019 were (1.058±0.232), (1.100±0.272), (1.108±0.266), (1.122±0.273) and (1.147±0.298) μg/mL respectively, and there were significant differences among groups (P < 0.05); the mean MICs of ICU were (1.159±0.303), (1.253±0.344), (1.320±0.331), (1.413±0.289) and (1.451±0.278) μg/mL respectively, there were significant differences among groups (P < 0.05); the mean MICs of non-ICUs were (0.995±0.134), (1.005±0.135), (1.005±0.091), (1.016±0.155) and (1.006±0.142) μg/mL respectively, there were no significant differences among groups (P>0.05). The mean MICs between ICUs and non-ICUs in the same year of 2015-2019 were all significantly different (all P < 0.05); proportion of MIC ≥ 1.5 μg/mL of vancomycin against MRSA had an increasing trend year by year. Conclusion Vancomycin-resistant MRSA was not found in Xuzhou in 2015-2019; vancomycin has MIC drift to MRSA, which mainly comes from ICUs. MRSA strains with vancomycin MIC ≥ 1.5 μg/mL and infected patients in ICU should be given stress surveillance and active treatment to prevent infection outbreak.