Obesity is an independent risk factor for venous thromboembolism and ischemic heart disease. Optimal dosing strategies for heparin in obese patients are limited, as this population is mostly underrepresented in clinical trials. We evaluated the therapeutic efficacy and safety of unfractionated heparin dosing protocols when used in obese patients. A retrospective review of treatment effects was performed to analyse patient specific data regarding the use of therapeutic heparin in patients divided into four weight groups (<100, 100 to <125, 125 to <150 and ≥150 kg). Patients received heparin via the dosing protocols approved by the institution's Pharmacy and Therapeutics (P&T) committee. Demographics, heparin protocol used, heparin dosage, therapy duration, laboratory values and indicators for bleeding complications were reviewed for adult patients receiving heparin for more than 48 h. Two hundred and forty patients were analysed, including 60 patients in each weight group. A significant difference was found across the groups in time to therapeutic activated partial thromboplastin time (aPTT) (P = 0.002) and mean heparin dosage at first therapeutic aPTT based on total body weight (units/kg per h) (P < 0.001). The mean first therapeutic heparin dose was approximately 16.0 units/kg per h in the less than 100 kg group and 11.3-13.0 units/kg per h in larger weight groups. The incidence rates of haemorrhagic complications appeared similar across the groups. Total body weight is the best predictor of a patient's requirement of heparin, but heparin infusion rates should be reduced in obese patients. Our study results showed that patients with at least 150 kg of body weight required 11.3 ± 2.7 units/kg per h on average to achieve a therapeutic aPTT.