The aim of this study was to evaluate relationships between free flap compromise and perioperative risk factors. A retrospective review was conducted for 237 patients who underwent 247 microvascular free flap reconstructions after head and neck ablative surgery. Twenty-one (8.5%) cases of free flap compromise due to a vascular obstruction were identified, and 11 flaps were lost (4.5%); an overall success rate of 95.5%. A significant correlation was found between diabetes mellitus and free flap compromise (p = 0.048). Preoperative irradiation was also found to influence free flap compromise, but with borderline significance (p = 0.052). However, multivariate analysis revealed a significant association between free flap compromise and diabetes mellitus [odds ratio = 4.9 (95% CI 1.1-22.8, p = 0.041)]. The presence of diabetes mellitus may require more attention to improve patient management and free flap outcomes.