Performing a sequential third free flap for reconstruction of a head and neck defect after cancer resection can be challenging, and the problem is further compounded in elderly patients. The outcomes in this clinical scenario are currently unknown and this study aims to compare the results in elderly patients with younger patients in a high-volume microsurgical unit. A retrospective review of 126 consecutive patients who had undergone three sequential free flap reconstructions after head and neck cancer was performed. The patients were divided into two groups - older or younger than 65 years old (n = 105 and n = 21, respectively). Patient demographics, intraoperative and postoperative outcomes were noted and analyzed. The overall flap success in this patient cohort was 94.4% (7 flap losses in 126 patients). Cardiovascular complications were significantly more common in the older group (19% vs. 1.9%, p = 0.001). Delirium occurred more frequently in the older group compared with the younger group (23.8% vs. 6.7%, p = 0.023). There were no significant differences regarding surgical complications. With adequate planning, a sequential third free flap can be performed safely and successfully in patients who are more than 65 years of age. Particular attention to the perioperative morbidity in elderly patients is crucial for successful outcomes.