Objectives <p>Intraoperative radiotherapy (IORT), has been debated regarding its long-term efficacy in breast cancer treatment. This study aimed to compare the differences among IORT, postoperative radiotherapy, and no radiation on long-term survival in early breast cancer patients undergoing breast-conserving surgery (BCS), as well as to investigate factors influencing the efficacy of different radiotherapy modalities.</p> Materials and methods <p>A cohort of 336,785 early-stage low-risk breast cancer women who underwent BCS from 2000 to 2019 was selected from the Surveillance, Epidemiology, and End Results database, with 2730 in the IORT group, 259,311 in the postoperative radiotherapy group, and 74,744 in the no radiation group. Propensity score matching balanced baseline characteristics. Kaplan–Meier method and landmark analysis were employed to calculate OS, while Cox proportional hazards regression analysis was conducted to identify risk factors for OS. Subgroup analyses explored factors impacting the efficacy of different radiotherapy modalities.</p> Results <p>In short-term survival within 48 months, IORT showed a more favorable prognosis than postoperative radiotherapy (<i>p</i> = 0.028); while there was no significant difference in prognosis between IORT and postoperative radiotherapy (<i>p</i> = 0.318), when beyond 48 months. The prognosis of the no radiation group was poorest. For patients under 50-years-old and hormone receptor-negative subtypes, radiotherapy did not significantly impact prognosis (<i>p</i> &gt; 0.05).</p> Conclusion <p>Breast cancer patients undergoing BCS significantly benefit from radiotherapy. Neither short-term nor long-term survival of IORT is inferior to postoperative radiotherapy, suggesting that IORT can be an effective alternative for early-stage breast cancer patients unsuitable for or unable to undergo postoperative radiotherapy.</p> Key Points <p><Emphasis Type="BoldItalic">Question</Emphasis> <i>As a relatively new radiotherapy approach, the long-term efficacy of IORT compared to postoperative radiotherapy and no radiotherapy remains controversial</i>.</p> <p><Emphasis Type="BoldItalic">Findings</Emphasis> <i>IORT may be superior to postoperative radiotherapy in short-term survival of 48 months, and is not inferior to postoperative radiotherapy in long-term survival</i>.</p> <p><Emphasis Type="BoldItalic">Clinical relevance</Emphasis> <i>This research hopes to contribute to the further exploration of IORT and offer improved treatment alternatives in early-stage breast cancer patients, particularly those who cannot undergo or face challenges with postoperative radiotherapy</i>.</p> Graphical Abstract <p></p>