Blood flow to a free flap may be impaired by thrombotic occlusion at the anastomosis or by microemboli occluding microvessels. The purpose of this study was to test the hypothesis that unfractionated heparin (UFH) or low molecular weight fractions of heparin (LMWH) could improve both the patency of microvascular anastomoses and microcirculatory perfusion. Sixty-six rats underwent orthotopic elevation of 3- x 10-cm epigastric free flaps. Animals received a single injection of either vehicle, UFH or LMWH, prior to microvascular clamp application and pedicle division. Anastomotic patency and tissue survival area were assessed on postoperative day 7. Anastomotic patency was significantly improved in both the UFH and LMWH groups. Total tissue survival area in those flaps with anastomotic patency was significantly improved in the UFH and the LMWH groups. Although both UFH and LMWH significantly elevated activated partial thromboplastin times (APTT) and anti activated clotting factor X (anti-Xa) activity over controls, UFH had its greatest effect on APTT, and LMWH on anti-factor Xa activity. Hematomas developed only in the UFH group. Thus, although both UFH and LMWH improved microcirculatory perfusion, as indicated by increased flap survival, only LMWH improved anastomotic patency while minimizing hemorrhage.