Delirium is categorized by acute changes in attention, cognition, and awareness that are not explained by pre-existing medical conditions. Its etiology remains poorly understood. Delirium occurs in around 21-25% of older patients after elective surgery and is associated with increased risk for post-discharge mortality, dementia, long-term cognitive decline, and other poor outcomes. APOe4, a neurodegenerative marker, has been associated with an increased risk of delirium; however, not all APOe4 allele carriers developed delirium, suggesting multifactorial mechanisms. The recent literature has suggested that chronic conditions are associated with the onset and progression of neurodegenerative diseases. It is not known whether the combination of chronic conditions and APOe4 infers a greater risk for delirium than either variable alone. This study investigates the association between APOe4 and postoperative delirium in the presence of chronic conditions through a secondary analysis of data collected from 2001 to 2014 at the University of California, San Francisco. The study included 351 non-cardiac elective surgery patients, aged 65 and older. Data collected include APOe4 allele status, medical history, and delirium status (Confusion Assessment Method). A total of 30.2% of patients in this sample were over the age of 75, 15.4% of patients had at least one APOe4 allele, 28.5% of patients had a Charlson Comorbidity Index (CCI) > 1, and 32.8% of patients developed postoperative delirium. There is an association between a higher number of comorbidities and postoperative delirium (OR = 1.70, CI = 1.03 - 2.82). After controlling for confounding variables (comorbidities and age), the association between APOe4 and postoperative delirium (OR = 0.50, CI = 0.21 - 1.23) was not statistically significant. This indicates that increased comorbidities and increased age have a greater impact on postoperative delirium than APOe4 in this cohort. This relationship can be used to inform clinical recommendations and aid in determining preventable risk.