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Introduction: Propofol is a commonly used sedative in mechanical ventilation, due to rapid onset and titratability. Its lipophilic properties result in high volume of distribution, causing accumulation in adipose tissue and pharmacokinetic differences in obese patients. Dosing adjustments based on body weight may help achieve sedation goals and reduce adverse events. Current literature is limited on optimal dosing across multiple body types for critically ill mechanically ventilated patients. This study describes the relationship between body mass index (BMI) and propofol dosing to achieve adequate sedation in obesity. Methods: This is a single-healthcare system, retrospective study of patients admitted to Methodist LeBonheur Healthcare between February 2023 and May 2025. Adult, mechanically ventilated patients that received propofol as the initial continuous infusion sedative within 6 hours of intubation were included. The primary outcome compared cumulative propofol doses (mg/kg, actual body weight) in first 24 hours of intubation between non-obese (BMI < 30 kg/m2), obese (BMI = 30-40 kg/m2), and morbidly obese (BMI >40 kg/m2) patients. Secondary outcomes included rate of sedation goal achievement in the first 24 hours and adverse effects. Results: Sixty-six patients met inclusion criteria and were 48% male, 71% Black/African American, on average 60 years old, and 80 kg. There was no significant difference between BMI groups for median propofol dose requirements over the initial 24-hour period following intubation: 42.6, 37.6, and 41.2 mg/kg for non-obese (n=39), obese (n=15), and morbidly obese (n=12) patients, respectively (p=0.767). Median Riker Sedation Agitation Scale scores in first 24 hours were -1, -2, and -2 for non-obese, obese, and morbidly obese patients, respectively (p=0.476). Time to sedation goal from propofol initiation was 5.9, 7.7, and 10.3 hours for these same groups (p=0.468). Incidence of systolic blood pressure < 90 mmHg were significantly lower in the morbidly obese group (p=0.038). Conclusions: As BMI increased, cumulative doses of propofol administered were similar across groups during the 24-hour post-intubation period. These results are preliminary, and further data collection will help inform appropriate weight-based dosing strategies for continuous infusion propofol.