Pain, dyspnea, and anxiety are common among patients with cancer, heart failure (HF), and chronic obstructive pulmonary disease (COPD), yet little is known about the severity of symptoms over time. To determine the prevalence, severity, burden, and predictors of symptoms during the course of hospitalization and at 2 weeks after discharge. A prospective cohort study. A large academic university. Patients were 65 years or older with a primary diagnosis of cancer, COPD, or HF. Daily living skills and depression were recorded at enrollment. Symptoms were assessed daily and 2 weeks postdischarge. At baseline, most participants reported moderate/severe pain (54%), dyspnea (53%), and anxiety (62%). Almost two-thirds (64%) had 2 or more symptoms at a moderate/severe level. The prevalence of moderate/severe symptoms decreased at the 24-hour assessment (pain = 42%, dyspnea = 45%, anxiety = 55%, burden = 55%) and again at follow-up (pain = 28%, dyspnea = 27%, anxiety = 25%, burden = 30%). While there was no association between primary diagnosis and symptom severity at baseline or 24-hour assessment, at 2-week follow-up, a higher percentage of patients with COPD had moderate/severe pain (54%, χ(2) = 22.0, P = 0.001), dyspnea (45%, χ(2) = 9.3, P = 0.05), and overall symptom burden (55%, χ(2) = 25.9, P = 0.001) than those with cancer (pain = 22%, dyspnea = 16%, symptom burden = 16%) or HF (pain = 25%, dyspnea = 24%, symptom burden = 28%). Predictors of symptom burden at follow-up were COPD (odds ratio [OR] = 7.5; 95% confidence interval [CI] = 2.0, 27.7) and probable depression (OR = 6.1; 95% CI = 2.1, 17.8). The majority of inpatients with chronic illness reported high severity of symptoms. Symptoms improved over time but many patients, particularly those with COPD, had high symptom severity at follow-up.