Postoperative or postinjury inflammation after knee surgery is a significant clinical challenge. Cytokines, particularly interleukin-1 (IL-1), released by inflammatory cells have been shown to have a role in cartilage homeostasis and tissue repair and fibrosis. Anakinra, an IL-1 receptor antagonist (IL-1ra), has shown promising results from its use in treating rheumatoid arthritis, juvenile inflammatory arthritis, and autoimmune inflammatory syndromes. We hypothesized that intra-articular anakinra injection may result in sustained improvements of persistent effusion of the knee joint refractory to other modalities. We retrospectively reviewed 6 patients (3 female, 3 male), ranging in age from 17 to 50 years, who underwent injection of intra-articular anakinra, 200 mg, between November 15, 2007, and April 29, 2010, for persistent effusions of the postoperative knee. All of the patients treated with intra-articular anakinra for persistent effusions failed conservative treatment with physical therapy, oral anti-inflammatory medication, and 4 of 6 patients failed prior corticosteroid injections. After intra-articular anakinra, 66% had improvement in knee arc of motion (15 to 30 degrees) and pain, and 5 of 6 (83%) had improvement in swelling. All of these patients were able to return to sports. We found intra-articular anakinra to be safe and effective in this small group of patients with persistent effusions. There were no adverse clinical reactions or infections. These findings provide support for further study of IL-1 inhibition in the management of postsurgical inflammation.