Objective To evaluate the clinical efficacy of early treatment with vancomycin in extremely severe burned patients, and provide references for anti-infection treatment of patients with extremely severe burn. Methods Clinical data of 15 patients with extremely severe burn and treated in the department of critical care medicine of a hospital were retrospectively analyzed, burn grade evaluation, infection index and trough blood concentration monitoring results of burn patients treated with vancomycin were statistically analyzed. Trough concentration prediction and Bayesian feedback method were adopted to compare the currently published population pharmacokinetic models of severe patients, optimal model for vancomycin treatment in extremely severe burned patients was screened out, administration of vancomycin in severely burned patients was optimized through Monte Carlo simulation. Results All 15 patients were administered vancomycin via continuous intravenous drip or pump, the average time of vancomycin administration was (11.07±1.71) days, and 79.31% of the steady-state trough blood concentrations met the standard (10-20 μg/mL), one patient developed renal toxicity during treatment. After screening, two-compartment model of severe patients reported in literatures was selected as the optimal model for vancomycin treatment in patients with extremely severe burns. Monte Carlo simulation results showed that 24 hours of continuous intravenous drip or pump administration was the best method for vancomycin treatment in patients with extremely severe burn, and the loading dose of 1.5 times of the normal dose can help quickly reach the effective concentration range. Conclusion The development of sepsis in extremely severe burned patients can be well controlled with early application of vancomycin. Continuously drip or pump administration combined with sufficient loading dose are critical to obtain best treatment of vancomycin.