The purpose of our work was to evaluate the efficacy of second breast-conserving surgery (BCS) and reirradiation with interstitial high-dose-rate (HDR) brachytherapy (BT) for the management of local recurrences. Between 1999 and 2010, fifteen patients initially treated for breast carcinoma by BCS and radiation therapy who had isolated intra-breast recurrence underwent second BCS and perioperative HDR multicatheter BT. Breast cancer related events, late side effects, and cosmetic results were assessed. At a median follow-up of 62 months (range: 11-127) second local recurrence has not occurred, yielding a 100% mastectomy-free survival. Four patients (27%) developed subsequent distant metastasis and died of breast cancer. The 5-year actuarial rate of disease-free and overall survival was 69% and 85%, respectively. Cosmetic results were rated excellent, good, fair, poor, and unknown in 1 (7%), 10 (66%), 2 (13%), 1 (7%), and 1 (7%) patients, respectively. Grade 2 fibrosis and skin toxicity occurred in 1 (7%) and 1 (7%) patients. Asymptomatic fat necrosis was detected in 9 (60%) women. No patient developed grade 3-4 late side effects. Second BCS followed by partial breast reirradiation is a safe and effective option for the management of selected patients developing intra-breast recurrence after previous breast-conserving therapy. Perioperative HDR BT may decrease the risk of second local relapse with acceptable cosmetic results and low rate of late side effects.