Background::Vancomycin treatment failure against vancomycin-susceptible gram-positive cocci is not rare in the intensive care unit (ICU). One of the reasons for this is the substandard drug trough concentration. We aimed to examine the hypothesis that the target serum concentration could be reached earlier with a loading dose of vancomycin.Methods::This retrospective cohort study was conducted at our ICU between June 2018 and June 2020 and involved patients who were suspected of having, or confirmed to have, gram-positive cocci infection and treated with vancomycin. One group of the patients was administered a loading dose of vancomycin (loading group) and compared with the group that did not receive a loading dose (control group). The baseline characteristics, vancomycin serum concentrations, and clinical outcomes were collected and analyzed.Results::Fifty-five patients were finally included, of which 29 received a loading dose of vancomycin. The serum concentration of vancomycin before the second dose was significantly higher for the loading group than for the control group (10.3 ± 6.1 mg/L n vs. 5.7 ± 4.4 mg/L, n P = 0.002). The results for both groups were similar before the fifth dose (12.4 ± 7.3 mg/L n vs. 10.3 ± 6.3 mg/L in the loading and the control groups, respectively; n P = 0.251). The 28-day mortality was lower for the loading group than for the control group (6.7% n vs. 34.6% in the loading and control groups, respectively; n P = 0.026). No significant differences were observed in serum creatinine (Cr) concentrations of the two groups.n Conclusion::With the loading dose of vancomycin, the target serum concentration of vancomycin may be reached earlier without increasing the risk of acute kidney injury.Trial registration::https://www.chictr.org.cn; ChiCTR2000035369“,”Background::Vancomycin treatment failure against vancomycin-susceptible gram-positive cocci is not rare in the intensive care unit (ICU). One of the reasons for this is the substandard drug trough concentration. We aimed to examine the hypothesis that the target serum concentration could be reached earlier with a loading dose of vancomycin.Methods::This retrospective cohort study was conducted at our ICU between June 2018 and June 2020 and involved patients who were suspected of having, or confirmed to have, gram-positive cocci infection and treated with vancomycin. One group of the patients was administered a loading dose of vancomycin (loading group) and compared with the group that did not receive a loading dose (control group). The baseline characteristics, vancomycin serum concentrations, and clinical outcomes were collected and analyzed.Results::Fifty-five patients were finally included, of which 29 received a loading dose of vancomycin. The serum concentration of vancomycin before the second dose was significantly higher for the loading group than for the control group (10.3 ± 6.1 mg/L n vs. 5.7 ± 4.4 mg/L, n P = 0.002). The results for both groups were similar before the fifth dose (12.4 ± 7.3 mg/L n vs. 10.3 ± 6.3 mg/L in the loading and the control groups, respectively; n P = 0.251). The 28-day mortality was lower for the loading group than for the control group (6.7% n vs. 34.6% in the loading and control groups, respectively; n P = 0.026). No significant differences were observed in serum creatinine (Cr) concentrations of the two groups.n Conclusion::With the loading dose of vancomycin, the target serum concentration of vancomycin may be reached earlier without increasing the risk of acute kidney injury.Trial registration::https://www.chictr.org.cn; ChiCTR2000035369