Thromboembolism is a common and occasionally catastrophic complication in patients with spinal cord injury and complete motor paralysis. We, therefore, evaluated the efficacy and safety of two prophylactic regimens, using heparin in either fixed doses of 5000 U given subcutaneously twice daily or in doses adjusted to prolong the activated partial thromboplastin time (APTT) to approximately 1 1/2 times control. Patients were monitored with daily clinical examinations, serial impedance plethysmography, and Doppler flow studies. All events suspected to be thromboembolic were confirmed by venography, ventilation-perfusion scans, or pulmonary angiography. Seventy-five patients were randomized, and 58 (29 in each group) either remained in the study for more than seven weeks or experienced a thrombotic or hemorrhagic event. Patients on the adjusted-dose regimen received a mean (+/- SD) of 13,200 +/- 2200 U of heparin per dose and had an APTT 1 1/2 times higher than those on the fixed-dose regimen. Thromboembolism was detected in nine (31%) of 29 patients randomized to the fixed-dose regimen and two (7%) of 29 on the adjusted-dose regimen. While no patient who received the adjusted dose and whose APTT reached the target level had a thrombosis, bleeding occurred in seven patients. No patient on the fixed-dose regimen bled. We conclude that patients with spinal cord injury who can be maintained on doses of heparin sufficient to prolong their APTT to 1 1/2 times control values will be spared thromboembolic complications, but these patients are at high risk of bleeding, especially if they have trauma to other tissues in addition to their spinal cord injury.