Objective Periprosthetic seroma is a rare complication of femoropopliteal bypass grafting. Periprosthetic seroma can be defined as the collection of non-infected serous fluid around a prosthetic arterial graft. There is a dearth of literature on how to manage periprosthetic seroma occurrence after femoropopliteal bypass especially in patients whose symptoms do not improve with typical conservative measures. Method/Results: This report highlights the case of a 70-year-old patient who had a femoropopliteal bypass using a 6 mm Propaten graft for peripheral arterial disease. The patient subsequently presented with leg edema. Leg ultrasound and computed tomography arteriogram showed a periprosthetic seroma with a patent graft. Patient was initially managed conservatively and semi-conservatively and ultimately with aggressive therapy utilizing exploration and surgical resection of the seroma capsule. Conclusion Only surgical resection of the seroma capsule produced definitive resolution of the seroma and symptoms. Thigh exploration and surgical resection can be considered as part of the management modalities of periprosthetic seroma occurring after femoropopliteal bypass especially in patients who do not respond to typical conservative measures such as elevation, compression stockings, and diuretics.