Background and purpose Randomized trials confirmed the efficacy and the safety of hypofractionated whole breast irradiation (HF-WBI) in patients with early-stage breast cancer. However, the role of HF-WBI in patients with DCIS after breast conserving surgery has not yet been clearly established in prospective randomized trials. The aim of this study was to evaluate if HF-WBI can be considered comparable to conventionally fractionated (CF)-WBI in DCIS patients. Materials and methods The analysis included DCIS patients from four Italian centers treated with CF-WBI 50 Gy/25 fractions or HFRT 40.5 Gy/15 fractions, without tumor bed boost. A propensity score matching (PSM) analysis was performed using a logistic regression that considered age, grading, presence of necrosis, resection margin status and adjuvant endocrine therapy. Results Five hundred twenty-seven patients was included (367 in the CF-WBI-group and 160 in the HR-WBI group). After 1:1 matching, 101 patients were allocated to the CF-WBI-group and 104 to the HF-WBI group. No correlation was observed between the type of RT schedule and LRFS (HR 1.68, 95% CI 0.82–3.45; p  = 0.152). After PSM, no statistical difference was observed between the two RT group (HR 1.11, 95% CI 0.40–3.04; p  = 0.833), with 3- and 5-years LRFS rates of 100% and 97.9% for CF-WBI and 95.6% and 94% for HF-WBI. Conclusion A short course of radiation therapy seems to be comparable to CF-WBI in terms of clinical outcomes. These data support the use of hypofractionated schedules in DCIS patients, but considering the remaining uncertainties.