This study was undertaken to evaluate the clinical characteristics and outcomes of patients with cancer requiring nonpalliative ventilatory support. This was a secondary analysis of a prospective cohort study conducted in 28 Brazilian ICUs evaluating adult patients with cancer requiring invasive mechanical ventilation (MV) or noninvasive ventilation (NIV) during the first 48 h of their ICU stay. We used logistic regression to identify the variables associated with hospital mortality. Of 717 patients, 263 (37%) (solid tumors = 227; hematologic malignancies = 36) received ventilatory support. NIV was initially used in 85 patients (32%), and 178 (68%) received MV. Additionally, NIV followed by MV occurred in 45 patients (53%). Hospital mortality rates were 67% in all patients, 40% in patients receiving NIV only, 69% when NIV was followed by MV, and 73% in patients receiving MV only (P < .001). Adjusting for the type of admission, newly diagnosed malignancy (OR, 3.59; 95% CI, 1.28-10.10), recurrent or progressive malignancy (OR, 3.67; 95% CI, 1.25-10.81), tumoral airway involvement (OR, 4.04; 95% CI, 1.30-12.56), performance status (PS) 2 to 4 (OR, 2.39; 95% CI, 1.24-4.59), NIV followed by MV (OR, 3.00; 95% CI, 1.09-8.18), MV as initial ventilatory strategy (OR, 3.53; 95% CI, 1.45-8.60), and Sequential Organ Failure Assessment score (each point except the respiratory domain) (OR, 1.15; 95% CI, 1.03-1.29) were associated with hospital mortality. Hospital survival in patients with good PS and nonprogressive malignancy and without tumoral airway involvement was 53%. Conversely, patients with poor functional capacity and cancer progression had unfavorable outcomes. Patients with cancer with good PS and nonprogressive disease requiring ventilatory support should receive full intensive care, because one-half of these patients survive. On the other hand, provision of palliative care should be considered the main goal for patients with poor PS and progressive underlying malignancy.