Background and Purpose: The purpose of this sequential intervention study was to determine the rate of local recurrences and the rate of distant metastases in patients with invasive breast cancer who had been treated with breast-conserving surgery and postoperative radiation therapy to the whole breast either with postoperative electron boost in group 1 or with intraoperative electron boost (IORT) in group 2. Patients and Methods: After breast-conserving surgery, 378 women with invasive breast cancer of tumor sizes T1 and T2 received 51–56.1 Gy of postoperative radiation therapy to the whole breast in 1.7-Gy fractions. 188 of those patients additionally received a postoperative electron boost of 12 Gy in group 1 from January 1996 to October 1998. Consecutively, from October 1998 to March 2001, 190 patients received intraoperative electron-boost radiotherapy of 9 Gy to the tumor bed in group 2. The groups were comparable with regard to age, menopausal status, tumor size, grading, and nodal status. All statistical tests were twosided. Results: During a median follow-up period of 55.3 months in group 1 and 25.8 months in group 2, local recurrences were observed in eight of 188 patients (4.3%) in group 1, and no local recurrence was seen in group 2 (p = 0.082). Distant metastases occurred in 15 of the 188 patients (7.9%) in group 1 and in two of the 190 patients (1.1%) in group 2 (p = 0.09). The 4-year actuarial rates of local recurrence were 4.3% (95% confidence interval, 1.8–8.2%) and 0.0% (95% confidence interval, 0.0–1.9%) and the 4-year actuarial rates of distant metastases were 7.9% (95% confidence interval, 4.5–12.8%) and 1.1% (95% confidence interval, 0.1–3.8%). Conclusion: Immediate IORT boost yielded excellent local control figures in this prospective investigation and appears to be superior to conventional postoperative boost in a short-term follow-up.