This prospective randomized trial compared an iridium-192 implant boost with a cobalt-60 external irradiation boost to the primary tumor site, in 255 patients with breast cancers 3-7 cm in diameter. All patients had a partial (> 50%) or complete response following primary external beam irradiation of 58 Gy to the whole breast, as well as irradiation to the axillary, supraclavicular and internal mammary nodes. Patients with clinically positive axillary nodes also received a cobalt-60 10-15 Gy boost to the inferior axilla. All patients had core biopsy only. Both groups were comparable in age, tumor size, node involvement, grade, and progesterone receptor levels. The boost dose was 20 Gy in both groups. At the median 8-year follow-up, the breast recurrence risk was 24% in the iridium group and 39% in the cobalt group (p = 0.02). When adjusted to other prognostic and treatment factors, the brachytherapy boost decreased the breast recurrence risk by 60%. The 8-year breast preservation rates were 81% and 67%, respectively (p = 0.024). Cosmetic outcome in both groups was evaluated in 120 patients with a minimum 3-year follow-up and was comparable in both groups. This study demonstrates that in selected patients with large tumors treated with irradiation alone, local control and breast preservation rates are improved by the use of brachytherapy to boost the primary tumor.