OBJECTIVE To determine the incidence and causes of perioperative complications in patients who undergo microvascular free flap procedures for reconstruction of the head and neck. METHODS Academic tertiary care medical center. METHODS A total of 400 consecutive microvascular free flap procedures were performed for reconstruction of the head and neck, with 95% of the defects arising after the treatment of malignancies. Flap donor sites included radial forearm (n = 183), fibula (n = 145), rectus abdominis (n = 38), subscapular system (n = 28), iliac crest (n = 5), and a jejunal flap. Patient-related characteristics (age; sex; diagnosis; comorbidity level; tumor stage; defect site; primary vs secondary reconstruction; and history of surgery, radiation therapy, or chemotherapy) and the incidence of perioperative complications were recorded prospectively over a 7-year period. RESULTS The perioperative mortality was 1.3%. Overall, perioperative complications occurred in 36.1% of all cases. Free flaps proved to be extremely reliable, with a 0.8% incidence of free flap failure and a 3% incidence of partial flap necrosis. Perioperative medical complications occurred in 20.5% of cases, with pulmonary, cardiac, and infectious complications predominating. Multivariate statistical analysis showed significant relationships between the incidence of perioperative complications and preoperative comorbidity level as indicated by American Society of Anesthesiologists (ASA) status (P =.02). CONCLUSIONS The present study confirms that free flaps are extremely reliable in achieving successful reconstruction of the head and neck. The incidence of perioperative complications is related to preoperative comorbidity level.