Objective: This study analyzes the failure of vancomycin blood trough concentration in critically ill patients and the influencing factors to provide a theoretical basis for its rational application. Methods: The data of 45 critically ill patients with infections induced by vancomycin treatment were retrospectively collected. Patients with a vancomycin blood trough concentration of <10 mg/L were assigned into the substandard group (n = 18), and those with a vancomycin blood trough concentration of >= 10 mg/L were assigned into the standard group (n = 27). Data such as age, gender, underlying diseases, treatment methods, albumin, creatinine, and glomerular filtration rate were analyzed, then multivariate analysis was performed using binary logistic regression. Results: The age, drug blood trough concentration, peak concentration, and blood creatinine concentration were significantly lower in the substandard group than in the standard group (p < 0.05), and the epidermal growth factor receptor (eGFR) level was significantly higher than in the standard group (p < 0.001). The rate of renal replacement therapy (RRT) was higher in the standard group than in the substandard group (p = 0.031). The factors with statistical differences between the two groups (age, blood drug peak concentration, eGFR, treatment methods, and continuous RRT) were used as the independent variables (X). Whether the blood concentration of vancomycin reached the standard was used as the dependent variable (Y). Binary multivari-ate logistic regression analysis was conducted. The results show that serum creatinine (p = 0.037, OR (odds ratio) = 1.248) and eGFR (p = 0.026, OR = 0.913) were independent influencing factors of vancomycin. Conclusions: The failure rate of vancomycin trough concentration in critically ill patients is higher. Serum creatinine and eGFR are independent associated factors for the substandard rate of vancomycin trough concentration.