Background: Re-operative parathyroidectomy in patients with recurrent or persistent hyperparathyroidism can be challenging. We review our experience to determine the optimal number of localization studies prior to re-operation. Methods: From 2001 to 2019, 251 patients underwent re-operative parathyroidectomy. Parathyroidectomies were stratified to 4 groups based upon the number of positive localization studies obtained: A) ZERO, B) 1-positive, C) 2-positive, D) 3-positive. Results: The overall cure rate was 97%, where 201 single gland resections, 23 two-gland resections, 22 subtotal/total, and 5 forearm autograft resections were performed. Thirty-two patients had no positive studies (A), 172 patients had 1-positive (B), 42 patients had 2-positive (C), and 5 patients had 3-positive studies (D). There was no difference in surgical cure rates between groups (p = 0.71). The majority of patients had one or no positive imaging studies yet almost all still achieved cure. Conclusion: Successful re-operative parathyroidectomy can be performed with minimal pre-operative scans in certain clinical contexts.