Objective To investigate the efficacy of vancomycin in the treatment of severe Gram-positive infections in very old patients and determine its effect on renal functions. Methods A total of 48 very old patients (age ≥80 years) with confirmed Gram-positive infection admitted in our geriatric unit from January 2007 to March 2014 were included in this study. They all received venous injection of vancomycin. Pathogen analysis was conducted for all the patients. Their signs and symptoms were observed before and after the treatment, as well as the clinical efficiency. And renal functions were evaluated dynamically during the treatment. Results The course of vancomycin treatment was averagely (18±9)d for the 48 patients, and the clinical efficiency was 72.92%. Among the 48 patients, 39 were infected by Gram-positive cocci in the bacterial culture or in smear test, and a total of 50 isolated strains were obtained. The bacterial clearance rate reached 82.25% after the vancomycin therapy. During the vancomycin treatment, 12 cases had renal toxicity, accounting for 25% of the total cases. Univariate logistic analysis showed that pre-treatment score of Acute Physiology And Chronic Health Evaluation (APACHE) Ⅱ (OR＝1.240, 95% CI: 1.061?1.449, P＝0.007）, mean trough concentration of vancomycin (OR＝1.268, 95% CI: 1.066?1.757, P＝0.014), the combined use of vasopressor agent (stratified into 3 groups, receiving no, small and large doses; OR＝4.33, 95% CI: 1.620?11.598, P＝0.0035), and the combined use of diuretics (stratified into 4 groups according to daily dose of furosemide, that is, ≤40, 41?80, 81?120 and ＞120mg/d; OR＝2.066, 95% CI: 1.189?3.589, P＝0.010) were risk factors for renal toxicity in the cohort during vancomycin treatment. Multivariate logistic regression analysis demonstrated that APACHE Ⅱ score ≥25 points, trough concentrations of vancomycin ≥18mg/L, and the combined use of diuretics (furosemide ≥40mg/d) would increase the risks of renal toxicity in the elderly patients. Conclusion Vancomycin is efficient in the treatment of severe Gram-positive infections in the elderly patients. But for them, the treatment leads to certain risk for renal toxicity, and the pre-treatment APACHE Ⅱ score ≥25 points, trough concentrations of vancomycin ≥18mg/L, and combined use of diuretics (furosemide ≥40mg/d) are independent risk factors for the toxicity.