BACKGROUND : Immediate breast reconstruction (IBR) improves psychosocial and quality of life outcomes. Post-mastectomy radiation therapy is indicated for patients with a high risk of locoregional recurrence including locally advanced tumours (≥ 5 cm) or greater than or equal to four axillary nodes positive for breast cancer and can be a relative contraindication to IBR. Administration of radiation therapy pre-operatively, analogous to neoadjuvant chemotherapy, may reduce time to completion of treatment and facilitate better access to IBR. METHODS : This is a prospective pilot study in a tertiary referral breast cancer unit, comparing surgical, pathological response and oncological outcomes and time to completion of therapy for a prospective group of patients who received neoadjuvant radiotherapy with a cohort of age- and stage-matched patients requiring post-mastectomy (± reconstruction) radiation between 2010 and 2016. RESULTS : Sixteen patients with locally advanced breast cancer underwent neoadjuvant radiation and were age- and stage-matched to 32 patients who received post-mastectomy radiation therapy (PMRT) between 2010 and 2016. Neoadjuvant radiotherapy resulted in shorter time between diagnosis and treatment completion (245.6 ± 44.2 days in the neoadjuvant group, 291.2 ± 36.7 days in the adjuvant group, p = 0.001). A higher proportion of patients undergoing neoadjuvant chemoradiation therapy underwent breast reconstruction (14/16 patients in the neoadjuvant group, 15/32 patients in the adjuvant group, p = 0.007) without an increase in complication rate (p = 0.117). There was a trend towards improved pathological complete response and survival in the neoadjuvant group. CONCLUSIONS : This pilot study confirms that neoadjuvant chemoradiation is a feasible way of delivering breast cancer treatment and may facilitate improved access to IBR.