BACKGROUND: Intraoperative radiation therapy (IORT) delivers the full course of radiation therapy during the initial surgical excision. In the early 2000s, IORT was a promising method of breast cancer treatment de-escalation, offering many advantages. This technique should have succeeded in the USA, but several factors hindered its widespread adoption. We report the results of our 15-year IORT registry trial and our reasons for halting the trial. PATIENTS AND METHODS: Patients with early-stage breast cancer were entered into an institutional review board (IRB) approved registry. They were analyzed by intention to treat and by various subgroups, including those who received local treatment to the area of the primary tumor only versus those who received additional whole breast treatment. RESULTS: A total of 1785 patients with 1828 early-stage breast cancers entered the registry. With a median follow-up of 85 months, the local recurrence rate (LRR) at 5-years for the entire cohort was 4.44%. Among 1527 who received local treatment only, the LRR at 5-years was 5.09% compared with 1.13% for 301 patients who received additional whole breast treatment (p = 0.001). For patients aged ≥ 65 with luminal A tumors ≤ 20mm, the 5-year LRR dropped to 2.32%. CONCLUSIONS: IORT is extremely convenient for the patient and offers many advantages when compared with other methods of partial or whole breast treatment. Overall, the LRR for IORT is 4-5 times higher than many competing forms of whole or accelerated partial breast irradiation but still relatively low. A more select choice of patients for IORT can lower the LRR. Following the decision by ASTRO in 2024 not to recommend IORT, and considering a number of other factors, our group made the decision to discontinue our IORT program.