Background: This study investigated the rate of contralateral papillary thyroid cancer (PTC) in low-risk PTC patients who had completion thyroidectomy, and were referred for radioactive iodine (RAI) therapy. The study sought predictors of contralateral disease and examined the impact of contralateral disease in RAI-treated patients. Methods: We reviewed 20 years of data from a prospective registry for 150 patients with PTC. These patients had undergone thyroid lobectomy, followed by completion thyroidectomy, and had been referred for RAI. Results: Of the 150 patients, 41% had PTC in the contralateral lobe. There was no difference in the rate of contralateral disease in low-risk patients (age <45 years, T1 tumors, lymph node-negative) compared with the remainder. There were no significant differences between patients with or without contralateral disease with respect to primary tumor size, mean age, time to completion thyroidectomy, or metastatic lymph node disease. Logistic regression analyses showed no histologic parameters that correlated with contralateral disease. There were no recurrence or survival differences in patients with or without contralateral disease after resection and RAI. Conclusions: The prevalence of tumor in the contralateral lobe of low-risk patients with PTC is significant and warrants consideration for completion thyroidectomy and radioiodine treatment. Our results, however, suggest that contralateral disease does not have an impact on recurrence or survival after treatment.