Objective. Anakinra has been shown to be successful in preventing and treating cardiovascular lesions both in experimental murine models of Kawasaki disease (KD) and in several studies of intravenous immunoglobulin (IVIG)and steroid-resistant patients with KD. This study was undertaken to determine the safety of blocking interleukin-1 in patients with IVIG-resistant KD. Methods. Sixteen patients were included in the present study. Patients with KD who were not responsive to 1 or more courses of 2 mg/kg of IVIG received anakinra by subcutaneous daily injections. The starting dose was 2 mg/kg of anakinra (4 mg/kg in patients who were age <8 months and who weighed ≥5 kilograms), and the dose was increased up to 6 mg/kg every 24 hours if the patient's body temperature remained >38°C, indicative of a fever. Treatment duration was 14 days. The last visit was on day 45. The primary outcome was abatement of fever. Secondary outcome measures included disease activity, coronary artery Z score, and C-reactive protein (CRP) levels. Results. Seventy-five percent of the patients in the intent-to-treat group and 87.5% in the per-protocol group became afebrile within 48 hours of the last escalation dose of anakinra. Reduction of disease activity by 50% was indicated on 93.3% of physician evaluations (95% confidence interval [95% CI] 68.1-99.8%) and on 100% of parent evaluations (95% CI 73.5-100%) of parent evaluations. CRP values normalized by day 30. At the initial screening, 12 of 16 patients had a maximum coronary artery Z score of >2, and 10 of 16 patients had a maximum Z score of >2.5. On day 45, 5 of 10 patients (50% [95% CI 18.7-81.3%]) and 6 of 12 patients (50% [95% CI 21.1-78.9%]) had achieved coronary artery Z scores of <2.5 and <2, respectively. Five serious adverse events were observed in 3 patients, but no serious infections or deaths occurred. Conclusion. Anakinra was well tolerated in the study patients and may have some efficacy in reducing fever, markers of systemic inflammation, and coronary artery dilatation in individuals with IVIG-refractory KD.