Carfilzomib has shown excellent outcomes for relapsed Multiple Myeloma. There have been increasing reports on cardiovascular adverse events. However, reports on severe pulmonary adverse events are rare. Our patient was a 79-year-old female, undergoing fourth-line therapy with Carfilzomib. At 24h after first administration, the patient was admitted to the emergency room complaining of dyspnoea. After a full recovery, the patient was re-evaluated. Since echocardiography showed normal cardiac function, Carfilzomib was re-initiated. At 24h after administration, the patient was re-admitted to the emergency room with severe dyspnoea, meeting criteria for ARDS. Despite mechanical ventilation, the patient developed cardiac arrest. Resuscitation was unsuccessful. Although patients might fully recover from a first episode of Carfilzomib-induced pulmonary toxicity, re-initiation of Carfilzomib is not recommended.