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Introduction: This study aimed to describe the incidence and identify risk factors associated with the development of propofol-induced hypertriglyceridemia in critically ill trauma patients. Methods: Three hundred and two patients admitted to the trauma ICU over a 16-month period were retrospectively evaluated. Patients received a continuous intravenous propofol infusion for at least 24 hours were included for study. Those without serum triglyceride concentration (TG) monitoring, without a Nutrition Support Service consult, younger than 18 years of age, who received less than 24 hours of propofol therapy, or with inadequate fluid intake and output documentation were excluded. Data were collected for the first 7 days of propofol therapy or until discontinuation of propofol, whichever came first. Hypertriglyceridemia (hyperTG) was defined as a serum triglyceride concentration (TG) > 400 mg/dl. Risk factors that potentially worsen TG were evaluated. Continuous data were expressed as median [25th, 75th percentile]. A p value < 0.05 was considered significant. Results: Of 100 evaluable patients, 25 patients developed hyperTG while receiving propofol. Four of these patients exhibited a TG > 1000 mg/dl. Median lipid intake from propofol was greater in those with hyperTG (0.22 [0.15, 0.45] g/kg/d vs 0.13 [0.1, 0.25] g/kg/d, p=0.002). Patients that developed hyperTG had a higher serum C-reactive protein (26.4 [20.1, 31] vs 19.7 [14.2, 28.4] mg/dl, p=0.018), lower serum prealbumin (3 [2.5, 8] vs 8 [5, 11] mg/dl, p< 0.001), higher serum creatinine (1.05 [0.81, 1.32] vs 0.83 [0.65, 1] mg/dl, p=0.031) and required a longer duration of nutrition therapy (19 [11, 26] vs 14 [7, 18] days, p=0.027) than those without hyperTG. Obesity, a history of hyperlipidemia, age, and other potential risk factors for hyperTG were similar between groups. Conclusions: HyperTG is common during propofol therapy and is reflective of higher propofol/lipid doses and is associated with greater inflammation, multi-system organ dysfunction, and severe critical illness requiring prolonged nutrition therapy. Early and frequent TG monitoring when receiving continuous propofol therapy is warranted.