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Background/Objectives: Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a potentially life‐threatening hypersensitive disorder. Cyclosporine has been indicated for adverse cutaneous drug eruptions. However, studies evaluating its clinical effectiveness in DRESS syndrome have been rare. This study aimed to evaluate the clinical efficacy of cyclosporine in DRESS syndrome compared to that of systemic corticosteroids. Methods: In the cyclosporine group, oral cyclosporine was administered twice a day for a total of 2–3 mg/kg/day for 1 week, and subsequently reduced to 1–1.5 mg/kg/day for extended treatment. In the corticosteroid group, intravenous or oral methylprednisolone was administered at 1–1.5 mg/kg/day for 1 week, with variable tapering plans. Laboratory changes before and after treatment, hospitalized days, treatment periods, and time to normalization from clinical manifestations in each group were statistically evaluated. Adverse effects of these regimens were observed during the entire treatment period. Results: Eighty patients were enrolled in this retrospective study. The cyclosporine and corticosteroid group had 27 and 53 patients, respectively. Total leucocyte and eosinophil counts, liver enzymes, and C‐reactive proteins were significantly decreased after treatment in both groups. There were no statistically significant differences observed in hospitalized days, treatment period, and time to normalization from clinical manifestations between the two groups. The corticosteroid group experienced relatively more adverse effects than the cyclosporine group. Conclusions: Cyclosporine was discovered to be clinically effective in DRESS syndrome and this study suggests that cyclosporine could be a feasible primary therapeutic option for DRESS syndrome. [ABSTRACT FROM AUTHOR]