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PURPOSE Post-mastectomy reconstruction using the deep inferior epigastric perforator (DIEP) flap is increasingly performed in breast cancer patients. The procedure induces large tissue trauma and it has been hypothesized that the release of growth factors, angiogenic agonists and immunomodulating factors may reactivate dormant micrometastasis. The aim of our study was to contrast the risk of breast cancer recurrence in patients undergoing DIEP reconstruction to patients treated with mastectomy alone. PATIENTS AND METHODS We conducted a retrospective nested case-control study. Cases were defined as breast cancer patients operated with delayed DIEP reconstruction at Karolinska University Hospital, Sweden, between 1999-2013. Three controls, defined as breast cancer patients operated with conventional mastectomy without delayed reconstruction, were matched to each case based on age, tumour stage and year of mastectomy. The primary endpoint was breast cancer-specific survival. Survival analysis was carried out by Kaplan–Meier survival estimates and Cox proportional hazard regression analysis. RESULTS In all, 254 cases and 729 controls were included and had a median follow up of 134 and 122 months, respectively (p=0.004). Breast cancer recurrence occurred in 50 (19.7%) cases and 174 (23.9%) controls, respectively (p=0.171). Ten-year breast cancer-specific survival was 90.7% for cases and 85.2% in controls (p=0.067). The corresponding figures for 10-year overall survival was 89.6% and 80.0%, respectively (p<0.001). Higher tumor stage and positive axillary lymph nodes, but not DIEP reconstruction, were independent risk factors for death due to breast cancer. CONCLUSION Our findings did not support the hypothesis that breast cancer patients undergoing DIEP reconstruction would have a higher rate of breast cancer recurrence than patients undergoing mastectomy alone. Citation Format: Adam H, Docherty Skogh A-C, Edsander Nord Å, Schultz I, Gahm J, Hall P, Frisell J, Halle M, de Boniface J. Risk of recurrence and death in breast cancer patients after delayed deep inferior epigastric perforator flap reconstruction [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P4-13-14.