A prospective study was performed to assess the clinical efficacy of intraoperative heparin combined with postoperative pneumatic foot compression and aspirin for thromboembolic disease prophylaxis after primary total knee arthroplasty (TKA). This group of 48 patients all had a primary TKA performed under epidural anesthesia. The cohort of patients was compared with a similar cohort of patients matched for age and comorbidity. The control group consisted of 61 patients (41 unilateral patients, 20 bilateral patients) with 81 TKAs who received epidural anesthesia and postoperative pneumatic foot compression and aspirin. The same surgeon and anesthesiologist performed all cases. All patients had the pneumatic foot compression device applied in the recovery room and received 325 mg of enteric-coated aspirin twice a day beginning the night of surgery. Venography was performed on the fifth postoperative day for both groups to determine the incidence of deep vein thrombosis (DVT). In the control group with postoperative pneumatic foot compression (group 1), the overall incidence of DVT was 27% (22 of 81), with 10% (8 of 81) major calf DVT and no proximal (popliteal or femoral) DVT. In the study group with intraoperative heparin and postoperative pneumatic foot compression (group 2), the overall incidence of DVT was 25% (12 of 48), with 8% (4 of 48) major calf DVT and no proximal DVT. There was no statistically significant difference between groups 1 and 2 for the incidence of overall DVT (P > .05) or major calf DVT (P > .05). No complications were associated with the use of intraoperative heparin or the pneumatic compression device, and no patient developed a symptomatic pulmonary embolism up to 3 months postoperatively. Although this study confirms that pneumatic foot compression combined with aspirin is an effective form of DVT prophylaxis after TKA, the added benefit of intraoperative heparin was not statistically proven. Although greater statistical power is needed to determine whether intraoperative heparin provides an added benefit, this study reveals a low incidence of DVT in TKA with this protocol.