To observe the changes of renal function in critically ill patients using vancomycin and analyze the renal protective effect of high dose vitamin C (VC) on vancomycin nephrotoxicity. Retrospective analysis was carried out to enroll the patients who were hospitalized in emergency intensive care unit (ICU) of Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January 2012 to October 2019. All patients were administered with vancomycin or VC infusion in addition. According to the infusion of vancomycin alone or in combination with VC, the patients were divided into vancomycin group and vancomycin in combination with VC group; vancomycin group was further divided into two groups according to before vancomycin or after vancomycin usage; combination group were further divided into two groups according to before VC use or after VC. The initial dosage of vancomycin was calculated according to the actual weight of the patient and adjusted according to the renal function. The dosage of VC was determined according to the disease severity of the patient, and the dosage range was 50-200 mg×kg-1×d-1, continuously infused into the body. The age, gender, weight and renal function etc. were recorded and analyzed. A total of 245 patients who met the requirements were included in the analysis. There were 127 patients in the vancomycin group and 118 patients in the combination group. The causes of patients admitted to ICU were pulmonary infection, sepsis, severe acute pancreatitis, etc. Among them, pulmonary infection accounted for 63.0% in vancomycin group, while severe acute pancreatitis accounted for 61.9% in combination group. The quick sequential organ failure assessment (qSOFA) score of combination group was significantly higher than that of vancomycin group [1.0 (0, 1.0) vs. 0 (0, 0.2), P < 0.01], its basic renal function was also significantly worse [serum creatinine (SCr, μmol/L): 98.0 (65.0, 178.2) vs. 56.0 (42.2, 71.0), blood urea nitrogen (BUN, mmol/L): 11.30 (6.48, 18.38) vs. 4.70 (3.45, 8.10), both P < 0.05], and the average daily dose of vancomycin was also significantly lower than that of vancomycin group (mg×kg-1×d-1: 23.0±9.4 vs. 26.6±8.5, P < 0.01). Compared with vancomycin before administration, the renal function was getting worse significantly after vancomycin administration [SCr (μmol/L): 68.0 (50.2, 104.5) vs. 56.0 (42.2, 71.0), BUN (mmol/L): 5.35 (3.75, 9.83) vs. 4.70 (3.45, 8.10), both P < 0.05]. Combination with VC significantly improved renal function compared with that before VC treatment [SCr (μmol/L): 79.0 (58.0, 129.0) vs. 98.0 (65.0, 178.2), P < 0.05; BUN (mmol/L): 9.60 (6.10, 18.30) vs. 11.30 (6.48, 18.38), P > 0.05] and shortened the length of ICU stay [days: 28.5 (14.8, 54.2) vs. 37.0 (25.0, 55.0), P < 0.01]. The incidence of drug-induced renal injury caused by vancomycin is high. Intravenous high dose VC can significantly reduce the nephrotoxicity of vancomycin and shorten the length of hospital stay. When vancomycin is used in critically ill patients, VC can be used in combination to reduce or avoid drug-induced renal injury, improve curative effect and reduce toxic effects.