The effect of obesity on the pharmacokinetics of enoxaparin is not clearly understood and traditional treatment doses in morbidly obese patients (body mass index [BMI] > 40 kg/m(2)) can lead to over anticoagulation. Our institution developed an inpatient protocol with reduced enoxaparin doses (0.75 mg/kg/dose based on actual body weight) for patients with a weight >200 kg or BMI > 40 kg/m(2). The primary objective was to determine if modified enoxaparin treatment doses would achieve therapeutic anti-Xa levels (goal range 0.6-1.0 IU/mL) in morbidly obese patients. Thirty-one patients were included in our study and had a median body weight of 138 kg (range 105-197) and a median BMI of 46.2 kg/m(2) (range 40.1-62). The initial peak anti-Xa levels were in therapeutic range in 15 of 31 patients (48 %) with an initial mean anti-Xa level of 0.92 IU/mL. Twenty-four patients (77 %) achieved therapeutic anti-Xa levels in goal range during their hospitalization, with a mean enoxaparin dose of 0.71 mg/kg. Bleeding and thrombotic events were minimal and all patients that achieved an anti-Xa level in goal range did so with a dose less than 1 mg/kg of enoxaparin.