The extent of surgical resection for differentiated carcinoma of the thyroid gland confined to one lobe remains controversial. Although primary tumor size and extrathyroid extension are associated with a poor prognosis, the presence of multifocal lesions is not associated with an adverse prognosis. Therefore, the role of lobectomy versus total thyroidectomy must be studied in a prospective, randomized trial. Due to the need for long-term follow-up, such a trial has not yet been undertaken. As an alternative to such a trial, we have identified 146 patients from a consecutive series of 931 previously untreated patients undergoing surgical treatment at 1 institution between 1930 and 1980. For this study of matched-pair analysis, 73 patients, aged 45 years or older, were matched in each arm for significant prognostic factors. One group underwent lobectomy, and the other group underwent total thyroidectomy. The 20-year survival rate in the lobectomy group was 82% compared with 73% in the total thyroidectomy group (p = not significant). The patterns of failure in these two groups of patients were examined. A comparison of the patients who underwent lobectomy with an unmatched group of patients who underwent lobectomy showed similar survival rates. On the other hand, unmatched patients undergoing total thyroidectomy had a poorer survival rate than the matched group. This signifies a more aggressive nature of disease in the unmatched group of patients undergoing total thyroidectomy. We therefore conclude that low-risk patients undergoing lobectomy are likely to do as well as those undergoing total thyroidectomy and without the increased risk of the morbidity of total thyroidectomy.