Background: Ageing, depression, and neurodegenerative disease are common risk factors for delirium in the elderly. These risk factors are associated with dysregulation of the hypothalamic-pituitary-adrenal axis, resulting in higher levels of cortisol under normal and stressed conditions and a slower return to baseline. Objectives: We investigated whether elevated preoperative cerebrospinal fluid (CSF) cortisol levels are associated with the onset of postoperative delirium. Methods: In a prospective cohort study CSF samples were collected after cannulation for the introduction of spinal anesthesia of 75 patients aged 75 years and older admitted for surgical repair of acute hip fracture. Delirium was assessed with the confusion assessment method (CAM) and the Delirium Rating Scale-Revised-98 (DRS-R98). Because the CAM and DRS-R98 were available for time of admission and 5 postoperative days, we used generalized estimating equations and linear mixed modeling to examine the association between preoperative CSF cortisol levels and the onset of postoperative delirium. Results: Mean age was 83.5 (SD 5.06) years, and prefracture cognitive decline was present in one-third of the patients (24 [33%]). Postoperative delirium developed in 27 (36%) patients. We found no association between preoperative CSF cortisol levels and onset or severity of postoperative delirium. Conclusions: These findings do not support the hypothesis that higher preoperative CSF cortisol levels are associated with the onset of postoperative delirium in elderly hip fracture patients.