Introduction: In intensive care unit (ICU) patients the number of studies on delirium and long-term outcomes is limited, and the results somewhat inconsistent. Unfortunately, all previous studies that reported increased mortality in delirious patients failed to adjust for severity of illness during ICU admission. The aim of this study was to assess the association of delirium in the ICU with mortality, long-term Health Related Quality of Life (HRQoL) and cognitive impairment, adjusting for severity of illness at ICU admission and during ICU stay. Methods: A prospective observational cohort study was conducted. We included ICU survivors who stayed in the ICU for more than one day, except for neurocritical care patients and patients who sustained deep sedation during the entire ICU admission. Twelve months after ICU admission, data on mortality was obtained and self-reported HRQoL and cognitive functioning were measured with the EuroQol-6D. Mortality was studied with Cox-regression analyses, HRQoL was analyzed using linear regression, and cognitive functioning was studied with multinomial logistic regression. All models were adjusted for gender, type of admission, the APACHE IV score and the cumulative SOFA score (without the central nervous system component) during ICU admission, as an estimate of severity of illness during ICU admission. Results: The study population consisted of 1101 patients admitted to a mixed medical-surgical ICU, of whom 412 persons (37%) were delirious during ICU stay. Of these, 198 (18%) patients died within 12 months after ICU admission. The response rate of the survey was 64%. After adjusting for confounding, including severity of illness during ICU admission, no significant association between delirium and long-term mortality was found (hazard ratio: 1.25; 95% confidence interval (CI) 0.92 to 1.69). After adjusting for the same covariates, delirium was not associated with HRQoL (β: -0.04; 95% CI -0.10 to 0.01). However, delirium remained significantly associated with mild and severe cognitive impairment when adjustments were made for confounders (odds ratio: 2.41; 95% CI 1.57 to 3.69 respectively 3.10; 95% CI 1.10 to 8.74). Conclusions: Our study suggests that delirium during ICU admission is not associated with long-term mortality or HRQoL after adjusting for relevant covariates, including severity of illness during ICU admission. By contrast, ICU delirium appears to be an independent risk factor for long-term cognitive impairment.