Summary: Background and aims: Recent research has suggested that high vitamin B12 levels may be associated with increased mortality after ICU admission. However, it is known that impaired liver function may lead to elevated B12 since B12 is metabolized through the liver, and therefore high B12 levels may serve as a proxy for poor liver function. The aim of this study is to assess the impact that liver function and liver disease have on the relationship between high vitamin B12 levels and mortality in the ICU. Methods: We performed an observational cohort study using ICU data that were collected from patients admitted to four ICU types (medical, surgical, cardiac care and cardiac surgery recovery) in one large urban hospital from 2001 to 2008. We analyzed the medical records of 1684 adult patients (age ≥18 years) who had vitamin B12 and liver function measurements up to 14 days prior to ICU admission or within 24 h after admission. Results: While we found an association between high B12 and mortality when we did not control for any potential confounders, after we adjusted for liver function and liver disease, no significant association existed between B12 and mortality using multivariable logistic regression (30-day mortality: OR = 1.18, 95% CI 0.81 to 1.72, p = 0.3890; 90-day mortality: OR = 1.20, 95% CI 0.84 to 1.71, p = 0.3077). Conclusions: Elevated B12 levels are not a significant predictor of mortality after ICU admission when liver function is controlled for, and may instead be a proxy for poor liver function. [Copyright &y& Elsevier]