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Objective: To examine the effects of vasopressors on free flap outcomes. Background: Most micro-surgeons avoid the use of vasopressors during free flap surgery due to concerns of vasoconstriction, which could potentially lead to vascular thrombosis and flap failure. Previous studies lack the statistical power to draw meaningful conclusions. Methods: All free flaps between 2004 and 2014 from a single institution were reviewed retrospectively. Vasopressors were given intraoperatively as an intravenous bolus when blood pressure dropped >20% from baseline. The timing of intraoperative vasopressor administration was divided into 3 phases: from anesthesia induction to 30 minutes before the start of flap ischemia (P1); end of P1 to 30 minutes after revascularization (P2); end of P2 to end of surgery (P3). Agents included phenylephrine, ephedrine and calcium chloride. Results: A total of 5671 free flap cases in 4888 patients undergoing head and neck, breast, trunk, or extremity reconstruction were identified. Vasopressors were used intraoperatively in 85% of cases. The overall incidence of pedicle compromise was 3.6%, with a flap loss rate of 1.7%. A propensity score matching analysis showed that intraoperative use of any agents at any time of surgery was not associated with increased overall pedicle compromise [51/ 1584 (3.2%) vs 37/792 (4.7%); P = 0.074] or flap failure rates [26/1584 (1.6%) vs 19/792 (2.4%); P = 0.209]. Rather, there was less risk of venous congestion [33/1584 (2.1%) vs 31/792 (3.9%); P = 0.010]. Conclusions: Intraoperative use of phenylephrine, ephedrine, or calcium chloride as an intravenous bolus does not increase flap compromise and failure rates in cancer patients. [ABSTRACT FROM AUTHOR]