The treatment of adult-onset Still’s disease (AOSD) aims to control systemic inflammation and prevent organ damage. Systemic inflammation can be controlled with corticosteroid (CS) monotherapy in most cases. However, symptoms often flare as CS is tapered, often requiring long-term CS treatment, with its associated risks of infection, cardiovascular disease, and osteoporosis. Disease-modifying antirheumatic drugs (DMARDs) are often used as CS-sparing agents; however, the choice of DMARD has been largely empirical. Methotrexate (MTX) is recommended as the first-line steroid-sparing drug due to its well-known efficacy and safety in rheumatoid arthritis (RA). When MTX treatment is unsuccessful in AOSD, the choice of a second-line drug has not been established. In RA, leflunomide (LEF) has been used as an alternative to or in combination with MTX. To date, there has been no adequate assessment of the combination of LEF and MTX in AOSD. Here, we report a case of refractory chronic AOSD successfully treated with the MTX-LEF combination.