The purpose of the study was to compare treatment outcomes in patients with breast cancer treated with partial breast irradiation (PBI) and of those treated with whole breast-radiation therapy (WBRT). We conducted a systematic review and meta-analysis of published randomized clinical trials comparing PBI versus WBRT. Primary outcome was overall survival and secondary outcomes were locally, axillary, supraclavicular, and distant recurrences. A search of the literature identified three trials with pooled total of 1,140 patients. We found no statistically significant difference between partial and whole breast radiation arms associated with death (OR 0.912, 95% CI 0.674-1.234, p = 0.550), distant metastasis (OR 0.740, 95% CI, 0.506-1.082, p = 0.120), or supraclavicular recurrences (pooled OR 1.415, 95% CI 0.278-7.202, p = 0.560). However, PBI was statistically significantly associated with an increased risk of both local (pooled OR 2.150, 95% CI, 1.396-3.312; p = 0.001) and axillary recurrences (pooled OR 3.430, 95% CI, 2.058-5.715; p < 0.0001) compared with whole breast-radiation. Partial breast irradiation does not seem to jeopardize survival and may be used as an alternative to whole breast-radiation. Nevertheless the issue of loco-regional recurrence needs to be further addressed.