Purpose: The purpose of this study is to evaluate the prevalence and the prognostic impact of antiphospholipid antibodies (aPL) in critically ill cancer patients. Methods: This is a prospective cohort study in adult patients admitted to the intensive care unit for more than 48 hours at a cancer center. Clinical and laboratory data including coagulation parameters were obtained. Cox proportional hazard models were used to identify predictors of 6-month mortality. Results: Ninety-five (solid tumor, 79%; hematologic malignancies, 21%) patients were included, and aPL were identified in 74% of them. Median Simplified Acute Physiology Score 3 and Sequential Organ Failure Assessment scores were 51 (37-65) and 5 (2-8) points, respectively. The most frequent aPL were lupus anticoagulant (61%) and anti-β2 glicoprotein I (32%). Vascular complications occurred in 18% of patients and were comparable between aPL+ and aPL− patients. Sepsis and need for renal replacement therapy were more frequent in aPL+patients. Hospital and 6-month mortality rates were 44% and 56%, respectively. Higher Sequential Organ Failure Assessment scores (each point) (hazard ratios [HR]=2.83 [95% confidence interval, 1.59-5.00]), medical admissions (HR=2.66 [1.34-5.27]), and D-dimer more than 500 ng/dL (HR=1.89 (1.04- 3.44]) were independently associated with mortality. After adjusting for these covariates, aPL status was not associated with outcomes (HR = 1.22 [0.60-2.47]). Conclusions: Lupus anticoagulants were frequent in critically ill cancer patients. However, they were not associated with medium-term survival in these patients.