Introduction: Emergency department (ED) stay and its associated conditions (immobility, inadequate hydration and nutrition, lack of stimulation) favor the development of delirium in vulnerable elderly patients. Poorly controlled pain, and paradoxically opioid pain treatment, has also been identified as a trigger for delirium. The aim of this study was to assess the relationship between pain, opioid treatment, and delirium in elderly ED patients. Methods: A multicenter prospective cohort study was conducted in four hospitals across the province of Québec (Canada). Patients aged 65 years old, waiting for care unit admission between February and May 2016, who were non-delirious upon ED arrival, independent or semi-independent for their activities of daily living, and had an ED stay of at least 8 hours were included. Delirium assessments were made twice a day for their entire ED stay and for the first 24 hours in the hospital ward using the Confusion Assessment Method (CAM). Pain intensity was evaluated using a visual analog scale (0-100) during the initial interview, and all opioid treatments were documented. Results: A total of 338 patients were included; 51% were female, mean age was 77 years (SD: 8). Forty-one patients (12%) experienced delirium during their hospital stay occurring within a mean delay of 47 hours (SD: 19) after ED admission. Among patients with pain intensity 60, 22% experienced delirium compared to 10.7% for patients with pain <60 (p<0.05). No significant association was found between opioid consumption and delirium (p=0.22). Logistic regression controlling for age, sex, ED stay duration, and opioids intake showed that patients with pain intensity 60 are 2.6 (95%CI: 1.2-5.9) more likely to develop delirium than patients who had pain <60. Conclusion: Severe pain, not opioids, is associated with the development of delirium during ED stay. Adequate pain control during the hospital stay may contribute to the decrease of delirium episodes.