Background Perforator flaps minimize abdominal site morbidity during autologous breast reconstruction. The purpose of this study was to assess whether the number of perforators harvested influences the overall deep inferior epigastric perforator (DIEP) flap survival and flap-related complications. Methods A retrospective review was performed of all DIEP flaps performed at the Hospital of the University of Pennsylvania from 2006 to 2011. The outcomes assessed included flap loss and major complications. We compared flaps by the number of total perforators (1-4) and then carried out a subgroup analysis comparing flaps with one perforator to flaps with multiple perforators. Lastly, we conducted a post-hoc analysis based on body mass index (BMI) categorization. Results Three hundred thirty-three patients underwent 395 DIEP flaps. No significant differences were noted in the flap loss rate or the overall complications across perforator groups. However, the subgroup analysis revealed significantly higher rates of fat necrosis in the case of one-perforator flaps than in the case of multiple-perforator flaps (10.2% vs. 3.1%, P=0.009). The post-hoc analysis revealed a significant increase in the flap loss rate with increasing BMI (<30=2.0%, 30-34.9=3.1%, 35-39.9=3.1%, >40=42.9%, P<0.001) in the DIEP flaps, but no increase in fat necrosis. Conclusions This study demonstrates that the number of perforators does not impact the rate of flap survival. However, the rate of fat necrosis may be significantly higher in DIEP flaps based on a single perforator. Multiple perforators should be utilized if possible to decrease the risk of fat necrosis.