Cryptogenic organizing pneumonia (COP) generally responds well to corticosteroids with a favorable outcome. However, it can rapidly worsen and lead to respiratory failure that is refractory to corticosteroids. Adjunctive drugs have been used in refractory cases with various outcomes, but treatment experience is still lacking. We present a case of rapidly progressive COP accompanying air leak syndrome, which showed no prompt response to corticosteroids alone but gradual improvement with the addition of cyclosporine and macrolide. This case report supports the existing literature suggesting that an early therapeutic trial of this drug combination might be considered in COP patients whose condition worsens despite corticosteroid administration.