Abstract Introduction: The indications for postmastectomy radiation therapy (PMRT) have expanded over the past decade. Plastic surgeons are reluctant to perform an immediate reconstruction followed by radiation because of their perception this sequence results in worse results. This study examines the relationship between the use and sequencing of radiation therapy on complication rates and patient satisfaction following reconstrucion.Methods: A retrospective chart review was performed of all women at an academic institution who underwent mastectomy and reconstruction from 1999-2006. The 769 reconstructed breasts were separated into 4 groups: PMRT prior to delayed reconstruction (n = 60); immediate reconstruction then PMRT (n = 56); reconstruction without PMRT (n = 540); and reconstruction after breast-conserving therapy with RT (BCT-RT, n = 113). The median length of follow-up was 44 months. All operative complications were categorized into early (≤90 days) or late. A questionnaire based on the Michigan Breast Reconstruction Outcomes Study assessed general and aesthetic satisfaction (response rate, 73.2%). Dichotomous variables were evaluated using the Fisher's exact or chi-squared test; statistical significance was set at p <0.05.Results: The overall complication rate for patients having PMRT (given before or after reconstruction) was higher than for patients with reconstruction only (36% vs. 27%, p = 0.048). The overall complication rate for women receiving PMRT then reconstruction was lower than for reconstruction then PMRT, although this was not statistically significant (28% vs. 45%, p = 0.068). Patients having reconstruction then PMRT had increased overall and late complication rates compared to patients having reconstruction only (45% vs.27.%, p = 0.006; 34% vs. 21%, p = 0.023, respectively). Results were similar when subdivided by the kind of reconstruction, except for increased late complications for patients having implant/expanders who had reconstruction then PMRT (62%, 8/13) compared to reconstruction alone (20%, 26/129) (p=0.003). General satisfaction was similar among all four groups. Aesthetic satisfaction was significantly lower in the PMRT then reconstruction group, compared to reconstruction only (48% vs. 65%, p = 0.029). Patients who underwent reconstruction then PMRT had similar aesthetic satisfaction compared to patients having reconstruction only (62% vs. 65%).Conclusions: Patients who have reconstruction prior to PMRT have increased overall and late complication rates compared to patients having reconstruction without radiation, but they have similar rates of general and aesthetic satisfaction. In contrast, patients who receive PMRT prior to delayed reconstruction have similar complication rates and general satisfaction levels to patients undergoing reconstruction only; however, the former patients report decreased aesthetic satisfaction. Patients requiring PMRT should consider both the risk of complications and likelihood of satisfaction in their decision-making process. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4102.