The objective was to determine the pharmacokinetics of tobramycin in critically ill adult burn patients and evaluate a variety of milligram per kilogram (mg/kg) total body weight (TBW) regimens to determine whether practical initial once-daily administration recommendations to attain desired plasma levels could be identified. A retrospective study was conducted in 58 eligible patients who received tobramycin and had at least one set of steady-state levels from which pharmacokinetic parameters could be determined using standard first-order pharmacokinetic equations. Classification and Regression Tree analysis was used to identify whether tobramycin clearance changed with time postburn. Monte Carlo Simulation was used to evaluate initial mg/kg TBW dosing regimens to determine whether a clinically useful once-daily tobramycin recommendation could be made. Tobramycin clearance was significantly greater for patients ≤45 days postburn vs patients >45 days postburn. Once-daily tobramycin dosing for patients ≤45 days postburn of 10 to 13 mg/kg TBW and for patients >45 days postburn of 8 to 10 mg/kg TBW provided levels similar to those known to be effective in nonburn injury patients. Once-daily tobramycin dosing recommendations for burn patients were determined. Variability in pharmacokinetics in this population and change in pharmacokinetics with time postburn injury necessitate monitoring of tobramycin levels to ensure targets are met and maintained.