Background Systemic juvenile idiopathic arthritis (sJIA) is a serious disease with significant morbimortality. Management of sJIA has improved dramatically over the last decade, especially with IL-1 receptor antagonists (IL-1Ra), but treatment remains heterogeneous. In this study, we described the evolution of patients with sJIA treated with IL1Ra, mainly as first-line therapy. Methods In this single-center retrospective observational study, we included all patients with sJIA treated with anakinra (ANK) between 2006 and 2020. Results Twenty-four patients received ANK after a median delay of 28 days (range 0–2070 days) after the diagnosis of sJIA. The median follow-up time was 2.37 years (range 0.49–10.75 years). Only 7/24 (29%) patients received corticosteroids. Inactive disease was observed in 18/24 (75%) patients at 3 months. Remission was observed in 19/23 (83%) patients at 1 year. At last available follow-up, 16/24 (67%) patients were in remission attributable to ANK and treatment-free remission was observed in 12/24 (50%) patients. Remission attributable to ANK was obtained in 12/15 (80%) patients treated with ANK within the first 3 months of the disease versus 4/9 (44%) patients treated after 3 months (p = 0.1). An initial White Blood Count ≥ 20 G/L was associated with remission attributable to ANK (p = 0.03). The only death occurred in a patient with a long-standing disease before ANK initiation and was attributable to the disease. Adverse events observed included ear, nose and throat infections and one transient liver cytolysis. Conclusions ANK in sJIA allows rapid remission with few adverse events. Their early use, as a firts-line therapy would allow rapid remission while avoiding the side effects of corticosteroids. Trial registration: retrospectively registered.