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Background/Objectives: The perioperative interplay between blood pressure, vasopressors, and macrocirculation is well established. However, in the context of free flap surgery, the potential impact of these factors on microvascular flow remains elusive. The aim was to evaluate the impact of norepinephrine administration on the microcirculation of free flaps. Methods: Postoperative systolic blood pressure (sBP), norepinephrine infusion rates (NIRs), and free flap microcirculation were monitored prospectively and analyzed retrospectively in patients receiving free flap surgery who required postoperative intermediate (IMC) or intensive care (ICU). Blood flow, hemoglobin oxygenation (SO 2 ), and relative hemoglobin levels (rHbs) were measured over a period of 24 hours post-anastomosis by laser-doppler flowmetry and white light spectroscopy using the "Oxygen to See" device (O2C, LEA Medizintechnik, Gießen, Germany). Multivariate analysis was performed to determine the impact of NIR on microvascular flow, adjusting for several confounding factors. Subgroup analysis was conducted by categorizing into three groups based on patients' postoperative sBP. Results: Flaps were performed in 105 patients with a mean age of 61.46 ± 16.29 years. Postoperatively, an increase in microvascular flow over time was observed across all free flaps, while NIR decreased and sBP maintained stable values. Multivariate analysis revealed that the time post-anastomosis (B = 3.76, p < 0.001), SO 2 (B = 0.55, p < 0.001), rHb (B= -0.79, p < 0.001), female gender (B = 29.25, p = 0.02), and no previous radiation therapy (B = 41.21, p = 0.04) had a significant impact on postoperative microvascular flow in free flaps. NIR, sBP, smoking status, old age, and ASA score showed no significant impact on free flap flow. Further, NIR showed no significant impact on microvascular flow in any of the subgroups investigated. Conclusions: These findings support the safety of using norepinephrine for maintaining stable blood pressure without compromising microvascular flow, offering valuable guidance for postoperative management., Competing Interests: The authors declare no conflict of interest.