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Purpose To investigate the impact of organizational characteristics and processes of care on hospital mortality and resource use in patients with cancer admitted to intensive care units (ICUs). Patients and Methods We performed a retrospective cohort study of 9,946 patients with cancer (solid, n = 8,956; hematologic, n = 990) admitted to 70 ICUs (51 located in general hospitals and 19 in cancer centers) during 2013. We retrieved patients’ clinical and outcome data from an electronic ICU quality registry. We surveyed ICUs regarding structure, organization, staffing patterns, and processes of care. We used mixed multivariable logistic regression analysis to identify characteristics associated with hospital mortality and efficient resource use in the ICU. Results Median number of patients with cancer per center was 110 (interquartile range, 58 to 154), corresponding to 17.9% of all ICU admissions. ICU and hospital mortality rates were 15.9% and 25.4%, respectively. After adjusting for relevant patient characteristics, presence of clinical pharmacists in the ICU (odds ratio [OR], 0.67; 95% CI, 0.49 to 0.90), number of protocols (OR, 0.92; 95% CI, 0.87 to 0.98), and daily meetings between oncologists and intensivists for care planning (OR, 0.69; 95% CI, 0.52 to 0.91) were associated with lower mortality. Implementation of protocols (OR, 1.52; 95% CI, 1.11 to 2.07) and meetings between oncologists and intensivists (OR, 4.70; 95% CI, 1.15 to 19.22) were also independently associated with more efficient resource use. Neither admission to ICUs in cancer centers compared with general hospitals nor annual case volume had an impact on mortality or resource use. Conclusion Organizational aspects, namely the implementation of protocols and presence of clinical pharmacists in the ICU, and close collaboration between oncologists and ICU teams are targets to improve mortality and resource use in critically ill patients with cancer.