Occasionally acute respiratory failure (ARF) develops in patients with connective tissue disease (CTD), but the etiologies of ARF in these patients are not fully elucidated. The objective of this study is to find out the causes of ARF leading to intensive care unit (ICU) admission in these patients and to assess their clinical outcome. The medical records of 1,870 consecutive patients admitted to the ICU in Seoul National University Hospital since January 2005-September 2008 were reviewed. A total of 66 patients with CTD were analyzed. The median age was 58 years, and 45 patients were women. The median length of ICU stay was 16 days with a median duration of mechanical ventilation support of 15 days. The distribution of underlying CTD was 17 patients with systemic lupus erythematosus; 15 with rheumatoid arthritis; 14 with systemic vasculitis; and nine with polymyositis-dermatomyositis. Pneumonia was the leading cause of ARF in 24 patients (36%). We could not identify the cause of ARF in 14. Other causes of ARF were acute pulmonary edema for nine patients, diffuse alveolar hemorrhage for eight and Pneumocystis pneumonia for four. Forty-one patients (62%) died during admission, and the mortality rate was the lowest in those with acute pulmonary edema. Use of norepinephrine was statistically higher in nonsurvivors. We could identify the cause of ARF leading to ICU admission in at least 80% of patients with CTD. However, these patients still showed a high mortality rate regardless of etiology. Their survival might be influenced by hemodynamic status.