Immediate reconstruction after mastectomy helps women manage the psychological impact of deforming surgery. Postmastectomy radiation therapy (PMRT) can negatively impact the aesthetic result after breast reconstruction. We performed this study to achieve a better understanding of how PMRT is used after reconstruction in our institution. We conducted a retrospective review of a prospectively maintained database of all women who underwent mastectomy for invasive breast cancer followed by immediate reconstruction from 2006 to 2017. Patients were divided into two groups depending on whether PMRT was included in their treatment, and we compared clinical and pathologic characteristics to determine which factors were likely to lead to PMRT. A total of 315 women treated with mastectomy and immediate reconstruction were identified. A total of 96 were treated with PMRT; 219 had mastectomy and immediate reconstruction without radiotherapy. Tumor characteristics, tumor stage, demographics, and comorbidities did not predict the use of PMRT. Neoadjuvant chemotherapy (NAC) was the most powerful predictor for using PMRT. In 47 of 81 (58%) patients treated with NAC, PMRT was used. Whereas 49 of 234 (21%) patients who did not receive NAC were treated with PMRT (P = 0.0001, risk ratio 2.77, 95 per cent confidence interval 2.03-3.77). In our institution, patients treated with NAC followed by mastectomy and immediate reconstruction are significantly more likely to receive PMRT. The increased use of PMRT after NAC should be factored into the preoperative discussion with patients choosing mastectomy and immediate reconstruction.