OBJECTIVE: Therapeutic advances have improved survival in patients with myeloma (MM) over the past decade. We investigated whether survival has also improved in critically ill myeloma patients. DESIGN: Retrospective study. SETTING: Intensive care unit. PATIENT: Consecutive myeloma patients admitted to a teaching hospital ICU between 1990 and 2006. We compared three year-of-admission groups (1990-1995, 1996-2001, and 2002-2006) that matched changes in myeloma treatment (chemotherapy only, stem cell transplantation, and new molecules, respectively). INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: We included 196 patients. Reasons for ICU admission and patient characteristics were similar across groups; however, less use of conventional chemotherapy and radiotherapy and greater use of steroids were noted in the more recent periods. Over time, vasopressors and invasive mechanical ventilation were used decreasingly, and noninvasive ventilation increasingly, to treat acute respiratory failure. Hospital mortality decreased from 75% in 1990-1995 to 49% in 1996-2001 and 40% in 2002-2006 (P = 0.0007). Mortality was associated with poor performance status [OR 2.27, 95% CI (1.04-4.99)], need for mechanical ventilation [OR 4.33, 95% CI (1.86-10.10)], need for vasopressors [OR 2.57, 95% CI (1.12-5.86)], and admission for an event related to myeloma progression [OR 2.77, 95% CI (1.13-6.79)]. ICU admission within 48 h after hospital admission was associated with lower mortality [OR 0.28, 95% CI (0.19-0.89)]. CONCLUSION: Hospital mortality decreased significantly over the last 15 years in myeloma patients admitted to the ICU. Risk factors for death were organ failure and poor chronic health status. Early ICU admission was associated with lower mortality, suggesting opportunities for further improving survival.