Background: The Emergency Medicine Palliative Care Access (EMPallA) trial is a large, multicenter, parallel, two-arm randomized controlled trial in emergency department (ED) patients comparing two models of palliative care: nurse-led telephonic case management and specialty, outpatient palliative care. This report aims to: 1) report baseline demographic and quality of life (QOL) data for the EMPallA cohort, 2) identify the association between illness type and baseline QOL while controlling for other factors, and 3) explore baseline relationships between illness type, symptom burden, and loneliness. Methods: Patients aged 50+ years with advanced cancer (metastatic solid tumor) or end-stage organ failure (New York Heart Association Class III or IV heart failure, end stage renal disease with glomerular filtration rate < 15 mL/min/m2, or Global Initiative for Chronic Obstructive Lung Disease Stage III, IV, or oxygen-dependent chronic obstructive pulmonary disease defined as FEV1 < 50%) are eligible for enrollment. Baseline data includes self-reported demographics, QOL measured by the Functional Assessment of Cancer Therapy-General (FACT-G), loneliness measured by the Three-Item UCLA Loneliness Scale, and symptom burden measured by the Edmonton Revised Symptom Assessment Scale. Descriptive statistics were used to analyze demographic variables, a linear regression model measured the importance of illness type in predicting QOL, and chi-square tests of independence were used to quantify relationships between illness type, symptom burden, and loneliness. Results: Between April 2018 and April 3, 2020, 500 patients were enrolled. On average, end-stage organ failure patients had lower QOL as measured by the FACT-G scale than cancer patients with an estimated difference of 9.6 points (95% CI: 5.9, 13.3), and patients with multiple conditions had a further reduction of 7.4 points (95% CI: 2.4, 12.5), when adjusting for age, education level, race, sex, immigrant status, presence of a caregiver, and hospital setting. Symptom burden and loneliness were greater in end-stage organ failure than in cancer. Conclusions: The EMPallA trial is enrolling a diverse sample of ED patients. Differences by illness type in QOL, symptom burden, and loneliness demonstrate how distinct disease trajectories manifest in the ED. Trial registration: Clinicaltrials.gov identifier: NCT03325985. Registered October 30, 2017.