BACKGROUND:: Lymphedema is characterized by fluid buildup and swelling, leading to skin fibrosis and recurring soft-tissue infections. There is a paucity of data examining the impact of lymphedema in total knee arthroplasty (TKA). The purpose of this study was to review the outcomes of TKA in patients with lymphedema compared with a matched cohort with primary osteoarthritis. METHODS:: One hundred forty-four knees underwent primary TKA with a preceding diagnosis of ipsilateral lymphedema. The mean follow-up was 7 years. A blinded 1:2 match of knees with lymphedema to a group of knees without lymphedema undergoing primary TKA was performed. Matching criteria included sex, age, date of surgery, and body mass index. The mean follow-up for the comparison cohort was 8 years. RESULTS:: Lymphedema increased revision hazard ratio [HR] 7.60; P < 0.001), reoperation (HR, 2.87; P < 0.001), and infection (HR, 6.19; P < 0.001) in addition to periprosthetic fracture (P = 0.04) and tibial component loosening (P = 0.01). The mean time to infection trended toward later time points in knees with lymphedema (19 versus 2 months, P = 0.25). DISCUSSION:: Lymphedema increased the risk of revision, reoperation, and infection. These data highlight the need for appropriate patient counseling and the need for further investigation into the effects of preoperative and postoperative optimization of lymphedema management in the TKA setting. LEVEL OF EVIDENCE:: Therapeutic Level III