Enoxaparin dosing in burn patients is challenging due to physiological changes following burn injuries that affect drug absorption, distribution, and clearance. The objectives of this study are to develop a population pharmacokinetic (PK) model for enoxaparin in burn patients, evaluate target attainment with current equation-based (EQ) dosing, and propose an optimized dosing regimen. Real-world data from 408 burn patients who received enoxaparin for thromboprophylaxis at the University of Utah Burn Center were analyzed, comprising 15,517 doses and 1,288 antiXa measurements. Only 56% of patients achieved the target antiXa range (0.2 – 0.4 IU/mL) approximately four hours after the third dose. A one-compartment PK model with first-order absorption and elimination best fit the data, with estimated apparent clearance (CL/F), volume of distribution (Vc/F), and absorption rate constant at 1.56 L/h, 22.1 L, and 1.10 1/h, respectively. Total body surface area (TBSA) and body weight significantly influenced clearance and distribution, while glomerular filtration rate had no notable impact. Simulations indicated that EQ dosing failed to achieve target levels after the first dose in 40% of patients, while the proposed regimen improved target attainment by more than 70%. This study underscores the limitations of EQ dosing, especially in patients with larger TBSA or higher body weight. In conclusion, a population PK model of enoxaparin was successfully developed for burn patients using real-world data and used to propose an alternative dosing regimen with higher target attainment in prophylaxis management.