The aim of this study was to verify the role of the venous drainage system in the pathogenesis of complications in microsurgical head and neck reconstruction. In a nonrandomized cohort study, 52 consecutive cases of complex head and neck microsurgical reconstruction were evaluated. The patients were divided in two groups based on the treatment: the deep (DVDG; n = 30) and superficial (SVDG; n = 22) venous drainage groups. The complications evaluated included vascular obstruction with partial or total loss of the microsurgical flap, inadequate healing (fistulas or suture dehiscence), and infections. The arterial anastomotic site, neoplastic recurrence, use of medications and neoadjuvant radiotherapy, flap selection, tumor histology, smoking/alcoholism, and systemic diseases had no effect on postoperative complications, while the venous component influenced the overall complication rate (chi-square test, P = 0.006). A protective effect was achieved in the DVDG when the overall complication rate was considered—relative risk (RR) 0.65, 95% confidence interval (CI) 0.45–0.94. The recipient vein should be the surgeon's main concern as it influenced the outcomes of patients undergoing complex microsurgical head and neck reconstruction. A protective effect was observed when the internal jugular vein drainage system was used for this purpose. © 2009 Wiley-Liss, Inc. Microsurgery 2009.