With growing interest in outpatient thyroidectomy, questions remain regarding the safety of this approach for high-risk patients, including individuals with obstructive sleep apnea, anticoagulant or anti-platelet use, substernal goiter, or Graves’ disease. This retrospective study evaluated 513 outpatient thyroidectomy cases at a high-volume endocrine surgery center, comparing postoperative complications and 30-day outcomes between high-risk and low-risk groups. Despite older age, higher comorbidity burden, and higher ASA class, high-risk patients demonstrated no significant increase in hematoma, recurrent laryngeal nerve injury, hypocalcemia, readmissions, reoperations, or ED encounters. Secondary analyses accounting for unplanned admissions and distance from the hospital confirmed similar safety profiles across groups. These findings support expanding outpatient eligibility among appropriately selected high-risk patients, emphasizing the importance of surgeon experience and structured perioperative protocols.