Fostamatinib is available in France since October 2021 for the treatment of adult chronic immune thrombocytopenia (ITP). French health authorities requested a 3-year, prospective, multicenter registry to provide real-world evidence about the effectiveness and safety of fostamatinib. Patients' characteristics, treatment response (ongoing exposure to fostamatinib and a platelet count ≥ 30 × 10⁹ /L with no rescue in the previous 4 weeks) after 3, 6, 12, and 24 months (M); bleeding; fostamatinib discontinuation; adverse drug reactions (ADRs) and other events of interest have been analyzed. In total, 164 patients were included (median age: 59 years; 55.5% women; 84.1% had previous bleeding; 30 had secondary ITP; 89.0% had chronic ITP). The median ITP duration was 7.2 years and the median number of previous ITP treatments was 6. The response rate was 44.0% (70/159) at M3, 41.9% (62/148) at M6, 32.4% (44/136) at M12 and 20.0% (21/105) at M24. Concomitant treatment (mostly TPO-RA) was used in > 60.0% of responders at each endpoint. The cumulative discontinuation rate at each endpoint was, respectively, 27.0%, 44.6%, 55.9%, and 76.2%. Seventy-one (43.3%) patients experienced at least one bleeding during fostamatinib exposure; none was fatal. One hundred adverse drug reactions (8 serious) were observed in 61 (36.7%) patients, including diarrhea in 28 (17.1%) patients, arterial hypertension in 17 (10.4%). Seven thrombosis (4.3%) and 40 infections (12 serious) were reported in 25 patients (15.2%), mostly in patients with known risk factors. In conclusion, fostamatinib in combination with TPO-RA should be considered in difficult-to-treat ITP patients. No new safety signal was observed.