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Introduction: Critical care pharmacist (CCP) services in the form of comprehensive medication management have been associated with reductions in mortality and length of stay. While known that high workloads of physicians and nurses reduce patient safety, an optimal CCP-to-patient ratio has not been determined. The purpose of this study was to establish the relationship of CCP-to-patient ratio with mortality. The hypothesis was that lower CCP-to-patient ratio would be associated with reduced mortality. Methods: In this 64-center, prospective analysis, CCPs collected data on CCP workload and ICU patients for 100 consecutive days followed by retrospective collection of patient characteristics (e.g., sequential organ failure assessment [SOFA] score, medication regimen complexity [MRC-ICU]) and outcomes. Adults admitted to an ICU without restrictions to care for at least 24 hours were included. Multi-variable logistic regression and Fine-Gray competing risks regression models accounting for ICU team workload (e.g., nurse/physician ratios) and patient characteristics (e.g., severity of illness, age, gender) were performed to characterize the relationship of CCP workload with mortality and hospital/ICU discharge, respectively. Results: A total of 213 CCPs collected data on 25,069 ICU patients. For every one patient increase in CCP-to-patient ratio, the odds of mortality increased by 0.72% (Odds Ratio 1.0072, 95% CI 1.0024-1.0120, p=0.003) after adjusting for SOFA score, institution type, ICU location, and MRC-ICU score. Patients with at least one day with no pharmacist coverage had an increased risk of mortality of 15.7% (95% CI 1.0282-1.3019, p=0.015). CCP-to-patient ratio was associated with reductions in hospital and ICU discharge rates (Hazard Ratio (HR) 0.993, p< 0.001 and HR 0.989, p< 0.001). Patients who had at least one day without a pharmacist also had a decreased rate of hospital and ICU discharge (HR 0.765, p< 0.001 and HR 0.619 p< 0.001). Conclusions: This study represents the largest, most comprehensive evaluation of CCP workload in the context of the ICU team. Results indicate that increasing CCP workload and lack of CCP coverage are associated with increased mortality. These results suggest work focused on optimizing CCP-to-patient ratio and consistency of CCP coverage can improve patient outcomes.