Purpose. The performance of a weight-based dosing protocol for unfractionated heparin (UFH) infusions using antifactor Xa monitoring was evaluated. Methods. The first 50 patients to receive a UFH infusion per the new protocol for over 24 hours, regardless of indication, were included in the analysis. All patients received a bolus dose of 26 units/kg, followed by an i.v. infusion of 15 units/kg/hr based on actual body weight, with no maximum dosage. Antifactor Xa levels were measured every 6 hours after infusion initiation and after every rate change until stable, defined as two consecutive results within the target range of 0.3-0.7 unit/mL, and every 24 hours thereafter. If a level was outside of the target range, the infusion rate was adjusted. Primary outcomes measured included the percentage of patients with a target level at the first test (obtained 6 hours after the start of therapy) and within the first 24 hours. The success of the protocol in obese patients versus nonobese patients was also analyzed. Results. Of the 50 patients enrolled, 26 (52%) achieved a target antifactor Xa concentration 6 hours after infusion initiation. Only 4 patients did not have an antifactor Xa concentration in the target range within 24 hours. Of the 17 patients weighing more than 100 kg, 16 (94%) had a value within the target range within 24 hours. Conclusion. A weight-based UFH dosing nomogram using antifactor Xa monitoring resulted in a high percentage of patients achieving target antifactor Xa values within the first 24 hours of therapy.