Objectives. Outpatient thyroid surgery is becoming increasingly common. The aim of this study was to clarify the principles for safe outpatient thyroid surgery and review our outcomes with the use of a protocol for outpatient thyroidectomy in a large patient cohort. Study design. A systematic analysis of a prospectively maintained database of outcomes of thyroidectomy in a tertiary endocrine surgery practice. Setting. Academic medical center. Subjects and methods. A protocol for outpatient thyroidectomy was conceived and refined over 3 years. A prospective analysis of all thyroidectomies accomplished by a single surgeon who used this protocol from May 2006 to November 2013 was then undertaken. Patient demographics, operative and pathologic data, admission status, complications, and readmission rates were recorded. Results. A total of 1,311 thyroidectomy procedures were performed during the study period, of which 1,026 (78.3 %) were conducted on an outpatient basis. The readmission rate for outpatients was 0.9%, with only 1 readmission in the last 200 procedures. Inpatients (which included patients in the 23-hour "observation" category) were readmitted more often than outpatients (3.5% vs 0.9%, P <.01). Outpatient management increased steadily throughout the study period (from 59.7% to 92.3%, P <.01), despite a larger mean nodule size and a greater rate of malignancy over time. There were no changes in the complication rate across the study timeframe except for the incidence of temporary hypocalcemia, which decreased over time (P <.01). Conclusion. Outpatient thyroid surgery is safe in appropriately selected patients using an optimized and systematic protocol.