PURPOSE Although delirium is known to negatively affect critically ill patients, little data exist on delirium in critically ill patients with cancer. METHODS We analyzed 915 critically ill patients with cancer between January and December 2018. Delirium screening was performed using the Confusion Assessment Method for the intensive care unit (ICU), performed twice daily. Confusion Assessment Method-ICU incorporates four features of delirium: acute fluctuations in mental status, inattention, disorganized thinking, and altered levels of consciousness. Multivariable analysis controlling for admitting service, pre-ICU hospital length of stay (LOS), metastatic disease, CNS involvement, Mortality Probability Model II score on ICU admission, mechanical ventilation, and others was performed to determine precipitating factors for delirium, ICU, and hospital mortality and LOS. RESULTS Delirium occurred in 40.5% (n = 317) of patients; 43.8% (n = 401) were female; the median age was 64.9 (interquartile range, 54.6-73.2) years; 70.8% (n = 647) were White, 9.3% (n = 85) were Black, and 8.9% (n = 81) were Asian. The most common cancer types were hematologic (25.7%, n = 244) and gastrointestinal (20.9%, n = 191). Delirium was independently associated with age (OR, 1.01; 95% CI, 1.00 to 1.02; P = .038), longer pre-ICU hospital LOS (OR, 1.04; 95% CI, 1.02 to 1.06; P < .001), not resuscitating on admission (OR, 2.18; 95% CI, 1.07 to 4.44; P = .032), CNS involvement (OR, 2.25; 95% CI, 1.20 to 4.20; P = .011), higher Mortality Probability Model II score (OR, 1.02; 95% CI, 1.01 to 1.02; P < .001), mechanical ventilation (OR, 2.67; 95% CI, 1.84 to 3.87; P < .001), and sepsis diagnosis (OR, 0.65; 95% CI, 0.43 to 0.99; P = .046). Delirium was also independently associated with higher ICU mortality (OR, 10.75; 95% CI, 5.91 to 19.55; P < .001), hospital mortality (OR, 5.84; 95% CI, 4.03 to 8.46; P < .001), and ICU LOS (estimate, 1.67; 95% CI, 1.54 to 1.81; P < .001). CONCLUSION Delirium significantly worsens outcome in critically ill patients with cancer. Delirium screening and management should be integrated into the care of this patient subgroup.