Background: The purpose of this study was to determine if radioguided parathyroidectomy (RGP) is effective for hyperparathyroidism (HPT) in the reoperative neck. Methods: We retrospectively reviewed all patients with HPT and a history of neck surgery who underwent RGP over a 7-year period. Data are reported as mean ± SEM. Results: We identified 110 patients with primary (n = 94), secondary (n = 7), or tertiary (n = 9) HPT who underwent 138 previous neck operations. The average hospital stay was 0.6 ± 0.1 days. The in and ex vivo counts obtained with the gamma probe were 310 ± 26 and 130 ± 13, respectively. The ex vivo percentage of background was 69% ± 9%, and virtually all resected parathyroids had ex vivo counts ≥20%. After RGP, 96% of patients were cured, and 5% experienced complications (all transient). Cure rates after RGP decreased as the number of previous neck operations increased (P = .002). Additionally, reoperative neck patients with single adenomas were more likely to experience cure than patients with hyperplasia (P = .02). Conclusion: These results illustrate that RGP is valuable in treatment of the reoperative neck. In addition, RGP allows similar lengths of stay, efficacy, and complication rates as those reported for patients undergoing initial parathyroidectomy. © 2009 Mosby, Inc. All rights reserved.