Simple SummaryImmediate free flap reconstruction is the method of choice after major head and neck cancer (HNC) resection, but this is frequently associated with long operating hours. This study investigated the feasibility of a two-staged, delayed reconstruction procedure in major HNC.AbstractA single immediate reconstruction with free tissue transfer is the method of choice after major head and neck cancer (HNC) resection, but this is frequently associated with long operating hours. Considering regulatory working hour constraints, we investigated whether a two-staged reconstructive approach with temporary defect coverage by an artificial tissue substitute would be feasible. HNC patients underwent either immediate or delayed reconstruction after tumor resection. Patients with delayed reconstruction received preliminary reconstruction with an artificial tissue substitute followed by definitive microvascular reconstruction in a separate, second procedure. Of the 33 HNC patients, 13 received delayed reconstruction and 20 received immediate reconstruction. Total anesthesia time (714 vs. 1011 min;p< 0.002) and the total duration of hospital stay (34 ± 13 vs. 25 ± 6 days;p= 0.03) were longer in the delayed reconstruction group. Perioperative morbidity (p= 0.58), functional outcome (p> 0.1) and 5-year postoperative survival rank (p= 0.28) were comparable in both groups. Delayed reconstruction after HNC resection was feasible. Perioperative morbidity, functional outcome and overall survival were comparable to immediate reconstruction.