Objectives: To identify factors independently associated with surgical complications in oncologic and reconstructive surgery and to examine sentinel lymph node (SLN) biopsy data, along with variables that are typically known prior to definitive resection, for their ability to impact the prediction of need for postmastectomy irradiation (PMRT). Design: Retrospective review. Setting: University hospital. Patients: Mastectomy patients with stage I to III breast cancer treated in 2000 to 2008. Main Outcome Measures: Complication rates of oncologic and reconstructive surgery requiring reoperation and clinicopathologic variables that independently predict complications and/or PMRT administration by multivariate analysis. Results: Among 100 of 302 mastectomy patients who underwent PMRT, complications occurred in 44% who underwent immediate breast reconstruction (IBR) and 7% who did not (P < .001). Postmastectomy irradiation independently predicted the occurrence of a complication (odds ratio, 3.3; P < .001). Implants were removed in 31% of patients who underwent PMRT and 6% of patients who did not (P = .005). Three percent of patients with T2 or smaller tumors and zero positive SLN required PMRT. Among those with T2 tumors, 49% with a positive axilla lymph node underwent PMRT. Independent predictors of PMRT need were T2 vs T1 tumors, positive axillary lymph node status, and the number of positive SLNs, with odds ratios of 5.8 (P < .001), 14.5 (P < .001), and 2.1 (P = .001), respectively. Conclusions: Postmastectomy irradiation was associated with a high rate of surgical complications and implant loss among patients who underwent IBR. Determining the number of positive SLNs prior to definitive resection and reconstructive operations may reduce complications and implant loss by guiding surgical decision making. Patients with a negative SLN are unlikely to require PMRT. Those with positive SLN(s) are high-risk IBR candidates with a quantifiable PMRT risk.