Acute respiratory failure that requires invasive mechanical ventilation is a leading cause of death in critically ill cancer patients. The aim of this study was to evaluate the outcome and prognostic factors of patients requiring invasive mechanical ventilator for acute respiratory failure, within 1 month of ambulatory chemotherapy for solid cancer. A retrospective observational study of patients who underwent ambulatory chemotherapy at Samsung Medical Center, between January of 2007 and April of 2009, was employed for this study. A total of 51 patients met the inclusion criteria and were included in the study. The median age was 65 years (25-87) and the majority of the patients were male (n = 38, 74.5%). There were 42 patients (82.3%) with lung cancer. The most common cause of acute respiratory failure was pneumonia (n = 24, 47.1%), followed by acute respiratory failure due to extra-pulmonary infection, drug-induced pneumonitis, alveolar hemorrhage, and cancer progression. The intensive care unit (ICU) mortality was 68.6% and the most common cause of death in the ICU was uncorrected cause of acute respiratory failure. Before adjustment for others factors, prechemotherapy Eastern Cooperative Oncology Group (ECOG) Performance Scale (PS) (P = 0.03), Sequential Organ Failure Assessment score (P = 0.01), and anemia (P = 0.04) were significantly associated with ICU mortality. However, when adjusted for age, sex, and Acute Physiologic and Chronic Health Evaluation II score, only poor ECOG PS (≥2) was significantly associated with ICU mortality [OR 6.36 (95% CI (1.02-39.5))]. The outcome of patients with acute respiratory failure needing invasive mechanical ventilation during ambulatory chemotherapy for solid cancer is poor. Prechemotherapy performance status is an independent predictor of mortality.