Unfractionated heparin infusion therapy is often administered using a weight-based dosing strategy for the treatment of venous thromboembolism. In the last several decades, the prevalence of obesity in the United States has increased significantly. The applicability of weight-based heparin dosing recommendations in the obese and morbidly obese population is uncertain, as limited data are available. We describe a 388-kg man who was started on an intravenous infusion of heparin according to hospital protocol for suspected pulmonary embolism. The patient was given a 5000-unit heparin bolus followed by an initial heparin infusion rate of 1500 units/hour, the maximum initial rate specified in the protocol. After additional infusion rate adjustments, a therapeutic activated partial thromboplastin time (aPTT) was reached 55 hours later with a heparin infusion rate of 3650 units/hour. Due to concerns of heparin-induced thrombocytopenia, heparin therapy was discontinued, and fondaparinux 5 mg/day was started. However, heparin therapy was restarted 4 days later for persistent, refractory hypoxemia and recurrent concerns of possible pulmonary embolism. During this second course, a therapeutic aPTT was achieved with a heparin infusion rate of 3550 units/hour. The patient developed bloody pulmonary secretions (with a therapeutic aPTT), necessitating the discontinuation of the heparin infusion. The patient later died after developing pulseless electrical activity. Standard weight-based heparin dosing protocols that specify maximum doses for initial bolus and infusion rates can result in significant delays in time to achieve therapeutic anticoagulation in the obese and morbidly obese patient. Despite limited data on heparin dosing in obesity, we recommend the use of a dosing weight to determine initial heparin dosing when treating venous thromboembolism in morbidly obese patients. It is reasonable to consider one of the following formulas: dosing weight = ideal body weight (IBW) + 0.3(actual body weight [ABW] - IBW), or dosing weight = IBW + 0.4(ABW - IBW).