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Breast reconstruction (BR) is considered to be adversely affected by radiotherapy (RT), particularly when an implant is used. The aim of this study was to compare clinical and patient-reported outcomes after expander-assisted latissimus dorsi breast reconstruction depending on the timing of RT.Patients undergoing BR over a 10-year period (follow-up mean, 56 [14–134] months) were divided into 3 groups. Group 1, RT after mastectomy and BR, Group 2, RT before mastectomy and BR, and Group 3, RT after mastectomy but before BR. The primary endpoints were early and late surgical interventions. Validated questionnaires were circulated to all study patients and matched controls.Three hundred thirteen patients underwent 389 BRs. One hundred eighteen patients received RT, of which 65 had undergone expander-assisted latissimus dorsi breast reconstruction. Both use and timing of RT influenced clinical outcomes. Overall, use of RT resulted in a 3-fold increase in complications (P = 0.003). Postreconstruction RT resulted in more than double the number of complications compared with prereconstruction RT (P = 0.008) and delaying BR until after mastectomy and RT reduced complications to levels observed in control patients (P = nonsignificant). Complications were halved in patients undergoing autologous LD reconstruction (P = 0.0001). Patient-reported outcomes were similar for emotional well-being, satisfaction, and shoulder symptoms, although a nonsignificant increase in chronic breast symptoms was reported by the RT group.The timing and type of LD reconstruction chosen by patients receiving RT has a significant impact on the risk of subsequent complications and unplanned interventions but has little impact on longer term patient well-being or satisfaction.