© 2015 Elsevier Inc. Background Thyroglobulin antibodies (TgAb) are produced by 10%-25% of thyroid cancer patients and interfere with thyroglobulin measurement, a marker of residual or recurrent cancer after surgery. Our purpose was to describe the TgAb resolution time course and the significance of persistent antibody elevation after thyroidectomy. Methods A database of 247 consecutive patients with TgAb measured preoperatively who underwent thyroidectomy for differentiated thyroid cancer between January 2007 and May 2013 was reviewed. Patients were stratified by TgAb status (positive or negative) and recurrence (defined as biopsy proven disease or unplanned second surgery). Survival and regression analysis was used to determine TgAb resolution time course. Log-rank was used to determine an association between persistent antibody elevation and recurrence. Results Of 247 patients (77% women, 23% men; mean 45.7 ± 1.0 y) with TgAb measured preoperatively, 34 (14%) were TgAb+ (â‰¥ 20 IU/mL; mean 298.1 ± 99.2 IU/mL). Median time to TgAb resolution was 11.0 ± 2.3 mo, and the majority resolved by 32.4 mo. Regression analysis of patients with antibody resolution yielded an average decline of -11% IU/mL per month ± 2.2%. Disease-free survival was equivalent between TgAb-positive and TgAb-negative groups (P = 0.8). In 9 of 34 patients, antibodies had not resolved at the last follow-up and imaging could not identify recurrent disease. Conclusions TgAb are common in patients with thyroid cancer but resolve after treatment at approximately -11% IU/mL per month from preoperative levels with median resolution at 11.0 mo. Persistently elevated levels after thyroidectomy were not associated with disease recurrence in our series.