Background: Symptomatic benign multinodular goiter (MNG) is extremely common in the north central United States. The extent of surgery for unilateral or bilateral disease is controversial. Bilateral resection should be associated with low recurrence rates, but potentially a higher technical morbidity. The long-term outcomes of patients with obvious unilateral MNG who had unilateral resection only is not commonly reported. To determine the optimal operation for patients with symptomatic MNG, we reviewed our single institutional results. Methods: From May 1994 through November 2004, 883 patients underwent a thyroid operation at our institution. Of these, 237 (27%) underwent thyroidectomy for MNG. One hundred forty patients underwent unilateral lobectomy and 97 underwent total thyroidectomy. Results: The mean age was 51 ± 1 years and 196 (83%) were female. With up to 145 months' follow-up, there was a higher recurrence rate in the lobectomy group (11% vs 3%; P = .029). However, patients in the lobectomy group had a much lower complication rate (2% vs 9%; P = .007). Importantly, in patients who underwent reoperation for recurrent MNG after lobectomy, the complication rate was low (5.5%) and not significantly higher than the initial surgery. Conclusions: In patients with symptomatic MNG, 89% of those who underwent unilateral resection did not require further surgery. Unilateral thyroidectomy was associated with lower morbidity than bilateral resection. Furthermore, those patients who required operation for contralateral recurrence did not experience a significantly higher operative morbidity. Therefore, these data convincingly support recommending unilateral thyroid lobectomy as the procedure of choice for patients with symptomatic unilateral MNG. © 2007 Mosby, Inc. All rights reserved.