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Background. Refractoriness to platelet transfusion is an understudied phenomenon in critically ill patients. Our objective was to evaluate the prevalence, risk factors, and clinical outcomes of platelet refractoriness among patients in a tertiary-care intensive care unit (ICU). Methods. A retrospective cohort study included all patients (age >14 years) who were admitted to a tertiary-care medical-surgical ICU between 2011 and 2016 and received ≥2 platelet transfusions during their ICU stay. We calculated platelet increment (PI) and corrected count increment (CCI). Results. A total of 267 patients were enrolled in the study, collectively receiving 1357 transfusions with a median of 4.0 (interquartile range: 2.0, 6.0) transfusions per patient. The median pretransfusion platelet count was 31000.0 × 106/L (interquartile range: 16000.0, 50000.0). The median PI was 6000 × 106/L. The prevalence of platelet transfusion refractoriness was 54.8% based on PI < 10000 × 106/L and 57.0% based on CCI <5000. Patients admitted under hepatology/liver transplant had the highest rates of platelet refractoriness (69.6%), while those under general surgery had the lowest rate (43.2%). Younger age, nontrauma admission, and larger spleen size were associated with platelet refractoriness. Finally, refractoriness was associated with increased length of stay in the ICU (p = 0.02), but not with mortality. Conclusions. Platelet transfusion refractoriness was highly (>50%) prevalent in ICU patients. However, it was not associated with increased mortality.