Context: Irisin is a recently identified myokine affecting metabolic and glucose homeostasis. However, the role of irisin in obesity and its metabolic consequences are controversial, and data in children are scarce. Objective: To study the relationships between irisin, insulin resistance, and puberty before and after weight loss in obese children with and without impaired glucose tolerance. Design: One-year follow-up study in obese children participating in a lifestyle intervention. Setting: Primary care. Patients: Forty obese children and 20 normal-weight children of similar age, gender, and pubertal stage. Intervention: A 1-year outpatient intervention program based on exercise, behavior, and nutrition therapy. Main Outcomes Measures: Fasting serum irisin, weight status (body mass index BMI SD score), and the following parameters of the metabolic syndrome: insulin resistance index (homeostasis model of assessment), blood pressure, and lipids. Results: The irisin levels were the highest in obese children with impaired glucose tolerance, followed by obese children with normal glucose tolerance, and levels were lowest in normal-weight children (P < .001). In a multiple linear regression analysis, baseline irisin was significantly associated with pubertal stage, high-density lipoprotein-cholesterol, and homeostasis model of assessment, but not to age, gender, BMI, or any other parameter of the metabolic syndrome. The irisin concentrations were significantly (P = .010) lower in the prepubertal compared to the pubertal children. In longitudinal analyses, changes of irisin were significantly associated with entry into puberty, change of fasting glucose, and 2-hour glucose in an oral glucose tolerance test, but not with change of BMI or any other parameter. Conclusions: Irisin levels are related to pubertal stage and insulin resistance but not to weight status in childhood.