Background: Enoxaparin is a low-molecular weight heparin (LMWH) commonly used for treatment of venous thromboembolism and acute coronary syndromes. The recommended dose for these conditions is weight-based (1 mg/kg) and doesn’t require dose-capping. However, previous studies have shown that in those with a body mass index (BMI) > 40 kg/m2, this dose results in supratherapeutic levels. Objective: This study investigated enoxaparin dosing in morbidly obese patients with a goal of identifying a dose with the greatest chance of producing favorable anti-factor Xa (anti-Xa) levels. Methods: This retrospective cohort study by electronic chart review was used to record data of patients who received enoxaparin with anti-Xa level monitoring between 2012 and 2017. The primary outcome was the enoxaparin dose that results in a therapeutic anti-Xa level (0.5–1.0 IU/mL) among three BMI groups. Secondary outcomes were bleeding and thromboembolic events. Results: Two hundred forty-one patients were included in the study, and 132 achieved a therapeutic dose. For those with a BMI of 40–50 kg/m2, the median therapeutic dose was 0.97 mg/kg every 12 h. In subjects with a BMI of 50–60 kg/m2, the median therapeutic dose was 0.70 mg/kg. Finally, the median therapeutic dose for subjects with a BMI over 60 kg/m2 was 0.71 mg/kg. In all three groups, 53–65% of patients had a supratherapeutic anti-Xa level while less than 10% had a subtherapeutic level. Relatively few patients (4.1%) experienced major bleeding and only one thromboembolic event was reported. Conclusion: Standard dosing of enoxaparin in morbidly obese patients will most likely lead to supratherapeutic anti-Xa levels and thus further investigation is warranted to better determine appropriate dosing.