Background: Challenging large soft tissue defects are typically treated with microvascular free tissue transfer; however, success has been noted with pre-expanded perforator flaps. Objective: To report outcomes and complications from pre-expanded perforator flaps. Methods: A retrospective chart review of patients undergoing tissue reconstruction with pre-expanded perforator flaps between 2014 and 2020. Data collection included flap type, defect characteristics, and complications. Results: All 29 patients had successful flap reconstruction without major complication. The median area of tissue defect was 17 × 13 cm2 (range 7 × 4 to 27 × 24 cm2). Mean tissue expansion period was 15.2 weeks (range 9-26 weeks). The most common flap was the pre-expanded internal mammary artery perforator flaps. Conclusion: The findings of this study suggest that combining tissue expansion with a perforator flap for large tissue reconstruction can be successful with limited complications. This technique may allow a larger pliable skin flap that deserves further investigation.