Life-threatening hypereosinophilic syndrome (HES) is a rare medical emergency with limited therapeutic options in corticosteroid-refractory cases. Preliminary reports suggest that Janus kinase inhibitors may be beneficial in eosinophil-associated disorders, including HES. We conducted a nationwide multicenter retrospective study to assess ruxolitinib. Thirteen patients with severe acute HES and organ- or life-threatening involvement were included, most requiring intensive care, with massive baseline absolute eosinophil counts (AEC, median 45 × 10⁹/L) and major involvement including eosinophilic myocarditis, ischemic strokes, and vascular thromboses. Ruxolitinib was initiated after a median of 7 days of corticosteroids. A rapid decline in absolute eosinophil counts was observed after initiation of ruxolitinib, with hematologic response rates of 54%, 85%, and 92% at Days 7, 14, and 30. Clinical improvement was observed across organ systems. Adverse events were manageable, although three deaths occurred during follow-up, only one of which occurred on ruxolitinib.