We retrospectively compared accelerated hypofractionation (AHF) with conventional fractionation (CF) in the radiation therapy (RT) for early-stage breast cancer patients. Three hundred seventy-nine early-stage (pT1-2 and pN0-1a) breast cancer patients who received RT with AHF after breast-conserving surgery (BCS) were included. These patients were matched with 379 corresponding patients who received BCS and RT with CF at a different center with respect to the year BCS was performed, patient age (-3 years), and cancer stage. The AHF regimen consisted of 39 Gy in 13 fractions to the whole breast and a consecutive boost of 9 to 12Gy in 3 to 4 fractions to the tumor bed. CF comprised whole-breast irradiation up to 50.4 Gy in 28 fractions and a boost of 9 to 14Gy in 5 to 7 fractions to the tumor bed. The median follow-up period was 75 months (range, 3.8-110.8 months). There was no statistically significant difference between the AHF and CF groups in terms of age distribution, T and N stage, resection margin, and histologic grade. There were 5 ipsilateral breast tumor relapse (IBTR) cases in the AHF group compared with 7 cases in the CF group. Seven and eight locoregional relapse (LRR) cases were observed in the AHF and CF groups, respectively. The 7-year rates of IBTR-free survival, LRR-free survival, and disease-free survival were 98.9%, 98.4%, and 97.1% in the AHF group and 98.1%, 97.9%, and 96.0% in the CF group, respectively (P>0.05). The incident rates of grade 3 edema, hyperpigmentation, or wet desquamation at the end of RT were higher in the CF group than in the AHF group (16.4% vs 0.2%, respectively; P<0.01). AHF RT of 39 Gy to the whole breast plus a 9-Gy boost in 16 fractions showed excellent tumor control and tolerable skin toxicity, a finding that is comparable to CF RT in patients with early-stage breast cancer.