Head and neck free-flap microvascular surgeries are complex and resource-intensive procedures where proper conduct of anaesthesia plays a crucial role in the outcome. Flap failure and postoperative complications can be attributed to multiple factors, whether surgical- or anaesthesia-related. The anesthesiologist should ensure optimised physiological conditions to guarantee the survival of the flap and simultaneously decrease perioperative morbidity. Institutions employ different anaesthetic techniques and results vary across centres. In our institution, two different total intravenous approaches have been in use: a remifentanil-based approach and a multimodal opioid-sparing approach, which is further divided into an opioid-free anaesthesia (OFA) subgroup. We studied every consecutive case performed between 2015 and 2022, including 107 patients. Our results show a significant reduction in overall complications (53.3 vs. 78.9%, p = 0.012), length of stay in the intensive care unit (3.43 ± 5.51 vs. 5.16 ± 4.23 days, p = 0.046), duration of postoperative mechanical ventilation (67 ± 107 vs. 9 ± 38 h, p = 0.029), and the need for postoperative vasopressors (10% vs. 46.6%, p = 0.001) in the OFA group (vs. all other patients). The multimodal and OFA strategies have multiple differences regarding the fluid therapy, intraoperative type of vasopressor used, perioperative pathways, and various drug choices compared to the opioid-based technique. Due to the small number of cases in our study, we could not isolate any attitude, as an independent factor, from the success of the OFA strategy as a whole. Large randomised controlled trials are needed to improve knowledge and help define the ideal anaesthetic management of these patients.