Background Therapy with intravenous unfractionated heparin improves clinical outcome in patients with active thromboembolic disease, but achieving and maintaining a therapeutic level of anticoagulation remains a major challenge for clinicians. Methods A total of 113 patients requiring heparin for at least 48 hours were randomly assigned at 7 medical centers to either weight-adjusted or non-weight-adjusted dose titration. They were separately assigned to either laboratory-based or point-of-care (bedside) coagulation monitoring. Results Weight-adjusted heparin dosing yielded a higher mean activated partial thromboplastin time (aPTT) value 6 hours after treatment initiation than non-weight-adjusted dosing (99.9 vs 78.8 seconds; P = .002) and reduced the time required to exceed a minimum threshold (aPTT >45 seconds) of anticoagulation (10.5 vs 8.6 hours; P = .002). Point-of-care coagulation monitoring significantly reduced the time from blood sample acquisition to a heparin infusion adjustment (0.4 vs 1.6 hours; P < .0001) and to reach the therapeutic aPTT range (51 to 80 seconds) (16.1 vs 19.4 hours; P = .24) compared with laboratory monitoring. Although a majority of patients participating in the study surpassed the minimum threshold of anticoagulation within the first 12 hours and reached the target aPTT within 24 hours, maintaining the aPTT within the therapeutic range was relatively uncommon (on average 30% of the overall study period) and did not differ between treatment or monitoring strategies. Conclusions Weight-adjusted heparin dosing according to a standardized titration nomogram combined with point-of-care coagulation monitoring using the BMC Coaguchek Plus System represents an effective and widely generalizable strategy for managing patients with thromboembolic disease that fosters the rapid achievement of a desired range of anticoagulation. Additional work is needed, however, to improve on existing patient-specific strategies that can more effectively sustain a therapeutic state of anticoagulation. (Am Heart J 1999;137:59-71.)