The current paper is a retrospective cohort study conducted on sixty-seven patients who underwent two-stage breast reconstruction over a 5-year period (2015–2020). Forty-one (61.2%) patients received radiotherapy (RT group), and twenty-six (38.8%) did not (non-RT group). Data regarding patients, oncological therapies, type of reconstruction, time of hospitalization, complications, and costs were collected. The statistical analysis was performed using IBM SPSS Statistics 25. General complications were noted for 18 patients (43.9%) in the RT group and for 7 patients (26.9%) in the non-RT group. Major complications were observed only in the first group (five patients–12.2%). The mean time of hospitalization in the RT group was 14.83 days for patients with complications versus 9.83 days for those without complications and 15.5 days versus 8.63 days, respectively, in the non-RT group. The mean cost for patients without complications was 235.64 euros, whereas the cost for patients with complications was 330.24 euros (p = 0.001). Radiation therapy can affect the overall outcome by increasing the risk of complications and increasing costs; however, our paper shows that the association of alloplastic reconstruction in patients with radiotherapy can be performed safely and with low costs in carefully selected patients.