BackgroundThe rate of bilateral mastectomy and bilateral breast reconstruction is increasing. The DIEP flap is an ideal method of breast reconstruction. The difference in risk of adverse outcomes between unilateral and bilateral DIEP flap breast reconstruction is unclear. The aim of this review is to investigate this relationship. MethodsAuthors searched Ovid EMBASE and MEDLINE from database inception to March 2012, for reports of DIEP flap breast reconstruction studies. After screening, data were extracted on flap-related, donor-site and systemic adverse events. Descriptive statistics were generated for all pooled data. We performed meta-analysis of direct comparisons to generate relative risk (RR) ratios with 95% confidence intervals (CI) using a random-effects model. ResultsOverall, 17 case-series of 2398 women were included. Compared with unilateral DIEP flap breast reconstruction, bilateral reconstruction was associated with a significantly higher risk of total flap failure (RR 3.31 [95% CI 1.50–7.28]; p = 0.003) and breast seroma (RR 7.15 [95% CI 1.21–42.36]; p = 0.03). Differences between other outcomes were non-significant, although descriptive analysis appeared to favour unilateral reconstruction. ConclusionsThe current literature related to DIEP flap breast reconstruction appears to be of low quality. However, this is the first systematic review confirming that bilateral DIEP flap breast reconstruction is associated with a significantly higher risk of total flap failure compared to unilateral DIEP flap breast reconstruction. This review will allow clinicians to better inform patients of the risks of adverse outcomes in DIEP flap breast reconstruction. It also highlights the need for higher quality research in this area.