Case histories of 140 patients who had mitral valve replacement with the Hancock xenograft were reviewed according to the incidence of thromboembolic complications. There were 16 patients with preoperative and/or postoperative low-output syndrome (Group A.) Eight of these patients died, and six had autopsies which showed major thrombi on the heterograft valve. In 126 long-term survivors (followed 1 to 33 months) nine thromboembolic events occurred (thromboembolic incidence 5.3 percent per patient-year). All patients with emboli were in atrial fibrillation. Additional predisposing factors included a history of systemic emboli and the presence of atrial clots at the time of surgery. The majority (7/9) of emboli occurred during the first 3 postoperative months. Two emboli occurred immediately following the operation (before oral anticoagulation therapy could have been begun). Five occurred in patients who were not on anticoagulation (Group B) and two occurred under warfarin treatment (Group C). There was no thromboembolic event in patients taking aspirin (Group D). It is concluded that hemodynamically stable patients have a decreased risk of thromboembolism and do not require anticoagulation. Patients with atrial fibrillation have an increased thromboembolic risk and should be on a regimen of warfarin for 3 months postoperatively and then on aspirin therapy.